Damaged Epidermis Research Articles

Histological evaluation of hyperpigmentation on female Filipino axillary skin1

Females in South East Asia (Thailand, Indonesia and the Philippines) show concern about dark areas of skin which develop in their underarms, but little is known about the features differentiating pale and hyperpigmented axillary skin in the general population. To investigate this, a histology study was undertaken in the Philippines to define the aetiology of underarm darkening, which is postulated to be a mild form of postinflammatory hyperpigmentation (PIHP). Punch biopsies were taken from dark and light axillary skin sites of 20 female subjects, of whom seven had hyperpigmented underarms, based on an instrumental (Mexameter MX-18, Courage and Khazaka Electronic GmbH, Cologne, Germany) measure, and 13 had not. Histological and immunohistochemical analyses were undertaken using a range of stains and antibodies, including haematoxylin-eosin for general histopathology, Masson-Fontana for melanin, anti-CD68 for monocytes and macrophages, Van Gieson's technique for fibrosis, anti-proliferating cell nuclear antigen for cell mitosis, and the melanocyte-specific immunostains, anti-tyrosinase and anti-tyrosinase-related protein 1. In most cases, dark skin sites from hyperpigmented panelists had increased intensity of Masson-Fontana, anti-tyrosinase and/or anti-TRP1 staining, indicative of melanocyte stimulation and increased melanin production. Furthermore, hair plucking emerged as a key stimulus to increased pigmentation. The trauma of hair plucking slightly increased the number of infiltrating mononuclear cells and macrophages that ingested melanosomes leaking from the damaged epidermis, more so in the skin of hyperpigmented panelists; this, in turn, potentially increases pigmentation. However, cell infiltration was focal, mainly near the plucked follicles, and not indicative of diffuse inflammation. The results from this study support the hypothesis that axillary darkening is mild PIHP, characterized by increased epidermal melanin, following stimulation or mild irritation of skin, with hair plucking as a key factor in this process.

Topo IIα reporter mice reveal proliferative regions in the epidermis and small intestine

We investigated topoisomerase IIα promoter activity in epithelia. In confluent human keratinocytes the promoter (−557 to +90 bp) was upregulated by oncogenic Ras. In transgenic mice expressing GFP via the promoter, GFP expression in undamaged epidermis was confined to growing hair follicles. GFP was also expressed in intestinal crypts. GFP expression was upregulated in epidermis following wounding or phorbol ester treatment. In each situation GFP expression correlated with high endogenous topoisomerase IIα expression and high proliferation. The mice therefore provide a useful model for non-invasive imaging of regions of high proliferation in normal or damaged epidermis.

Pre-harvest rindstain of ‘Encore’ mandarin: initial histological signs of epicarp disturbance and extent of the disorder

Pre-harvest rindstain in ‘Encore’ mandarin starts by the injury of a few epidermal cells. The connection between the damaged epidermis and the collapsed layers of flavedo, extending in parallel with rind surface was only visible on cross-sections containing the narrow zone of injured epidermal cells. The individual cell alteration including loss of membrane integrity and the accumulation of large amounts of osmiophilic materials in the cytoplasm are the result of a degrading process. Minute disruptions in the cuticle may provide shelters for resting forms of amoeboid or plasmodial-like organisms living on the rind. Our results suggest that these organisms could be involved in the disorder expression.

Stem cells in the skin: waste not, Wnt not.

Human disease results from loss of organ function. Whether the tissue failure results from infarction, infection, trauma, or congenital malfunction, the ideal treatment would be regrowth of a new organ or tissue to replace that which is lost or injured. Stem cell research holds the promise of developing such treatments for many life-threatening and debilitating diseases. Stem cells come in two basic types, unrestricted and restricted. Embryonic stem cells are totipotent, able to differentiate into all cell types characteristic of the species they are taken from. Adult stem cells are thought to be more restricted in their potential, functioning as the body’s natural source of cells for tissue homeostasis and repair. Although it seems unlikely that adult stem cells harvested from one tissue might be reprogrammed to take on the characteristics of a different cell type, several tantalizing results have encouraged researchers to consider this possibility. Before scientists can begin to define the limits of adult stem cell plasticity, they need to understand the signals that instruct multipotent cells to self-renew and differentiate within the lineages of their resident tissues. Skin is an excellent model system in which to explore these fundamental mechanisms, because skin keratinocytes are easily accessible and are one of the few adult stem cell types that can be maintained and propagated in vitro. These cells have already been engrafted long term to replace damaged epidermis on burn patients. Now skin biologists have begun to identify some of the key steps involved in generating a functional tissue from multipotent stem cells. The totipotency of embryonic stem (ES) cells, coupled with their ability to respond to morphogenic signals and differentiate into any desired cell fate, makes them an attractive starting place for cell replacement therapies. If stem cells derived from adult human tissues offer similar promise, this would circumvent many of the ethical and technical issues that cloud the ES cell field (Ferrari et al. 1998; Gussoni et al. 1999; Krause et al. 2001; Peterson 2002). In the past few years, researchers have claimed that mouse brain stem cells injected into irradiated recipient mice contribute to the recovering hematopoietic system (Bjornson et al. 1999), and conversely, some transplanted bone marrow stem cells reportedly differentiate into brain cells (Mezey et al. 2000). Even in human, female cancer patients receiving bone marrow transplants from male donors were found to have differentiated cells with male chromosomes in their cerebella, leading scientists to posit that transdifferentiation of donor hematopoietic stem cells may occur in brain tissue (Weimann et al. 2003). Although enticing, the seemingly extraordinary plasticity of adult stem cells has been met by critics who suggest that the reported transdifferentiation events may have arisen from fusion of stem cells with existing differentiated cells, or from injections of heterogeneous populations of incompletely characterized stem cells, rather than true reprogramming (Terada et al. 2002; Wagers et al. 2002; Ying et al. 2002). Advocates counter that tissue injury, which is present in clinical situations requiring treatment, increases the rate at which bone-marrow-derived stem cells transdifferentiate into other cell types such as muscle and neurons (Jiang et al. 2002; LaBarge and Blau 2002). As the controversy over stem cell plasticity continues, the potential for cell fusion or deregulated transdifferentiation raises other concerns, as cancerous cells may derive from somatic stem cells (Reya et al. 2001). The contention in the adult stem cell field reflects how little is known in a rapidly moving field whose potential impact on clinical medicine is high. A major challenge over the next decade will be to identify the molecular signals that regulate stem cell self-renewal, proliferation, and differentiation. Unless responding to injury, most adult stem cells typically divide infrequently to maintain homeostasis within their resident tissues. As a stem cell daughter commits to differentiate, it first enters a transient state of rapid proliferation (Fig. 1A). Following several cycles of division, the transiently amplifying cells withdraw from the cell cycle and execute a terminal differentiation program (Potten et al. 1979). Stem cell progeny differentiate in response to similar external and intrinsic signals experienced by their multipotent embryonic counterparts. Adult stem cells reside in specific niches. Corresponding author. E-MAIL fuchs@rockefeller.edu; FAX (212) 327-7954. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1086903.

Lymphoedema: Pathophysiology and management in resource-poor settings - relevance for lymphatic filariasis control programmes

Low cost reduction of morbidity in lymphoedema is an essential goal in the management of lymphatic filariasis. This review emphasises the role of movement and elevation, and refers to the literature on the effects of these on the venous and lymphatic system. The patient with lymphoedema becomes increasingly immobile and the affected limb is often in a permanently dependent position causing venous hypertension and resultant overloading of the failing lymphatics. The evidence that breathing exercises are important for reducing venous hypertension and inducing lymphatic flow is discussed.The contribution of a damaged epidermis to lymphatic failure is emphasised. Loss of barrier function encourages penetration of bacteria and stimulates repair mechanisms that generate cytokines, which, in turn lead to inflammation. Management programmes that improve the health of the epidermis play a part in reducing lymphatic load.In taking morbidity management of lymphoedema into the general health services there are benefits in promoting skin hygiene and self-help regimes that can ameliorate many diseases along with lymphoedema.

A histological study on the mechanism of epidermal nuclear elongation in electrical and burn injuries.

Epidermal nuclear elongation is one of the most important signs for the diagnosis of electrical injury. In this study, we investigated the mechanism responsible for this phenomenon by comparing the findings from burn injuries and those from contusions. Electrical and burn injuries were made in the dorsal skin of rats using energy ranging from 100 to 790 joules for electrical injury, and 170-690 joules for burn injury. Contusions were also made by compressing the skin with a vice. In electrical and burn injuries, the dermis under the epidermal elongated nuclei was homogeneous and without empty spaces between collagen bundles and the number of dermal fibroblasts per 0.01 mm2 below the damaged epidermis decreased significantly (P < 0.05). The incidence of this change correlated with the depth of denatured dermal collagen fibres and in both types of injuries, dermal cells had no nuclear antigenicity for ubiquitin. The width of the injured epidermis with nuclear elongation decreased significantly (P < 0.05) and the elongated nuclei were parallel to the basal membrane. In electrical injury however, nuclear elongation occurred more frequently near the external root sheath. Nuclear elongation of fibroblasts and external root sheath cells was also found, but those of sebaceous gland cells were not detected. Epidermal elongated nuclei were also found in contusions. The evidence strongly suggests that epidermal nuclear elongation in electrical and burn injuries is due to dermal expansion by heat.

Changes in the activity and pattern of hemolymph esterases in the larvae of wax moth Galleria mellonella L. (Lepidoptera, Pyralidae) during mycosis

The extended pattern of multiple esterase forms has been revealed in the hemolymph of wax moth Galleria mellonella larvae infected by the fungi Metarhizium anisopliae, Beauveria bassiana or Paecilomyces fumoso-roseus. The total esterase activity of the hemolymph also increases during mycosis. Mechanical damage of the cuticle, treatment with deltamethrin, and chilling of the caterpillars induced similar changes in the hemolymph pattern of esterase activity. Presumably, the changed spectrum and activity of the hemolymph esterases during mycosis is due to the damaged cuticle and epidermis cells.

Aging and the epidermal permeability barrier: Implications for contact dermatitis

Objectives : This report examines our present knowledge of the epidermal permeability barrier as it pertains to irritant contact dermatitis and discusses how altered barrier function may affect the clinical manifestations of irritant contact dermatitis in the aged. Conclusions : Altered barrier function affects the ability of an irritant to penetrate the stratum corneum and produce deleterious effects on both stratum corneum and epidermis. Moreover, a damaged epidermis can be expected to produce a defective stratum corneum, thus resulting in a vicious cycle. Furthermore, although basal transepidermal water loss has traditionally been used as an assessment of barrier function, evidence suggests that dynamic tests of barrier function are more reliable indicators of barrier function in the clinical setting of additive, repetitive, or chronic insults. Finally, barrier disruption per se has now been shown to produce both a cytokine response and an increase in epidermal Langerhans' cell density. Thus, barrier disruption not only alters penetrance of contactants, but also may prime the inflammatory response. Studies of aged epidermal permeability barrier function provide a greater understanding of the modified response to irritants in the aged.

Histological responses of port wine stains in brown skin after 578 nm copper vapor laser treatment.

The object of this study is to characterize the effects of epidermal melanin in brown skin on selective vessel damage by copper vapor laser radiation in port wine stain (PWS). STUDY DESIGN/MATERIALS, AND METHODS: We observed the histological changes of PWS in Korean patients who received copper vapor laser (578 nm) treatment over a range of energy densities (6-14 J/cm2) and exposure durations (30-200 ms). The nitroblue tetrazolium chloride (NBTC) staining method was used to differentiate between the blue-stained viable cells and the unstained thermally damaged cells. With Fontana-Masson stain, we found that Korean skin has more epidermal melanin than Caucasian skin. For energy densities greater than 6 J/cm2, epidermal damage was observed. At 6 and 8 J/cm2, the damage to the dermis was localized to the blood vessels and the perivascular tissue. The connective tissue between damaged vessels and epidermis was still viable. Energy densities above 10 J/cm2 produced a diffuse thermal necrosis. We conclude that vascular selectivity without epidermal damages cannot be achieved with a 50 ms exposure at 578 nm in the brown skin of Koreans. The energy density for clinical minimal whitening was 6-8 J/cm2, and the maximum penetration depth of these energy densities was 0.4 mm. We also found that the epidermal damage increased with increasing pulse widths at a fixed energy density (10 or 8 J/cm2) while the severity and depth of vascular damage decreased. These findings suggest that it is best to treat PWS with a copper vapor laser at the minimal pulse width and maximal power output possible at given energy density. We have demonstrated that the copper vapor laser treatment of PWS in the brown skin is not as selective as in white skin because of epidermal melanin.

Damage in apple (Malus domesticaBorkh) fruit exposed to different levels of rain acidity

SummaryThe effects of rain acidity on fruit of field-grown apple trees (Malus domestica Borkh) cv. Summerred were investigated. One group of four trees was exposed to ambient rainfall, while four other groups were covered with rain shields and received simulated rain consisting of deionized water or an acid solution at pH 5.6, 4.0 or 3.0. SEM examination showed alterations of the cuticular wax and russeting of the skin. Formation of a cambium, which in turn brought about the formation of a phellem layer as a substitution for the damaged epidermis and hypodermis, was evident. Necrosis and lesions on fruit mesocarp were also observed. Simulated acid rain at pH 4.0, and particularly at pH 3.0, damaged fruit and impaired its marketability. The acidity of ambient rainfall and simulated acid rain at pH 5.6 caused negligible damage.

Studies of the pathogenesis of orf virus infection in sheep

Damage to the skin is essential for the establishment of orf virus infection and the development of typical lesions. However, analysis of the pathogenesis of experimental lesions induced by viral challenge of mildly abraded skin, indicated that the virus does not establish in the damaged epidermis, but replicates in the cells of an underlying replacement epidermal layer derived from the walls of the wool follicles. The skin reaction consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillare of the dermis. Healing is then completed by the formation of a third epidermis derived from the deeper portions of the wool follicles. Previous cutaneous infection did not prevent reintroduction of the disease, even on the same area of skin although the lesions were less severe and persisted for a shorter period.

The BB-isoenzyme is a major component of creatine kinase in skin blister fluid.

We measured levels of creatine kinase and its three isoenzymes in serum and blister fluid from 16 healthy volunteers. The BB-isoenzyme was found to be the predominant form in blister fluid while only the MM isoenzyme was found in serum. The levels of BB-isoenzyme in blister fluid decreased as the blisters aged. The source of BB-isoenzyme in blister fluid is most probably the damaged epidermis.

Is there an optimal laser treatment for port wine stains?

Optimization of laser treatment of port wine stains (PWS) is discussed from the standpoint of heat production. Laser wavelength, irradiation time, heat conduction, and external epidermal cooling are the variables considered in conjunction with absorbing and scattering behavior of a PWS-model consisting of epidermis, dermis, and ectatic blood vessel. Ideal treatment is defined as minimal heating of the epidermis and upper dermis, but with irreversible damage to the capillary wall. The analysis shows that irradiation times of 1-10 ms in conjunction with external epidermal cooling may give optimal results. The wavelength of choice is 577 nm, followed by 540, 415, 560, and 500 nm (argon laser). The ruby and Nd-YAG lasers are predicted to damage the epidermis and dermis at all times when the capillary is coagulated. Concurrent cooling to prevent epidermal-dermal damage is also recommended here. The CO2 laser is predicted to be the worst laser and, according to our analysis, should not be used to treat PWS. Both upper dermal and capillary destruction can only result from heat conduction from the damaged epidermis and external cooling cannot be applied here.

Progression of thermal injury: a morphologic study.

The events that participate in the local pathophysiology of a burn would have not been completely described. This study defines the sequential morphologic changes following untreated partial-thickness burns. Guinea pigs received partial-thickness scald burns by 75 degrees C water immersion for 10 seconds. Skin samples were then obtained at 2, 8, 24, and 96 hours after the burn and examined by light and electron microscopy. A definite progression of the thermal injury was found, with maximum tissue destruction occurring 8 hours after the burn. At 24 hours after the burn, some improvement in the burn wound was noted, especially in the dermal microvasculature. At 96 hours, the damaged epidermis sloughed, exposing a dermis that contained areas resembling microabscesses.

The anaerobic fungi in rumen fibre digestion

Large populations of anaerobic fungi have been shown to colonize plant fragments in the rumen of cattle and sheep on fibrous diets. Plant material entering the rumen is rapidly colonized by flagellated zoospores that attach and produce hyphae that grow and penetrate deeply into the plant tissues. The growing fungus develops an extensive rhizoid for anchorage and supply of nutrients, and (later) a sporangium. Rupture of the sporangium and release of zoospores completes the developmental cycle. The fungi colonize mainly plant vascular tissues and highest numbers are found on stem fragments. The more fibrous the diet the greater the fungal population, and anaerobic fungi are absent from rumen contents of sheep grazing soft leafy plant materials. The major route of fungal invasion is via areas of damaged epidermis. The fungi can be grown in culture on a wide range of solid substrates. Cellulase activity has been demonstrated in anaerobic cultures containing strips of filter paper. Fungi similar to the rumen organisms have been shown to be present in the foregut and hindgut of a wide range of different types of herbivorous animals. The extent of colonization and growth on fibrous plant fragments suggests a significant role in cellulose digestion in the rumen. The ability of fungi to penetrate deeply into tissues not normally accessable to bacteria also suggest a special role for anaerobic fungi in rumen fibre digestion.

The control of epidermal mitotic activity in the mouse.

A study has been made of the abnormally high mitotic activity seen in mouse epidermis adjacent to a wound. Such activity is in the form of a gradient, no more than about 1 mm long, with the highest mitotic rate adjacent to the cut edge. It is shown that this gradient is not due to differential damage or to the effects of local hyperaemia. When the hypodermis and dermis are wounded from below, the overlying undamaged epidermis does not react by mitosis. Such a wound includes damage to the panniculus carnosus, the hair follicles and the sebaceous glands. It also involves hyperaemia and an invasion of leucocytes. It therefore appears that damage to the epidermis itself is necessary before an epidermal reaction can develop. Such a reaction could be due either to the secretion by the damaged epidermis of a mitosis stimulating ‘wound hormone' or to the local elimination of a normally present epidermal mitotic inhibitor. It was observed that when one side of the ear is wounded high mitotic activity develops in the opposite undamaged epidermis, which is less than 1 mm distant. In further experiments it was found that the greatest reaction in a sheet of undamaged ear epidermis is opposite the centre of an area from which the epidermis has been removed altogether. Since the area from which the epidermis was removed was 3 mm square, it is obvious that an epidermal ‘wound hormone' could not have been present in effective concentration in the central region, but the absence of an inhibitor which would normally have been present could explain the result obtained. It is therefore concluded that the gradient of epidermal mitotic activity adjacent to a wound may be inversely proportional to a gradient of mitotic inhibitor, which may cease to be produced within damaged cells and which may also diffuse away into the cavity of a wound. The question of the possible presence within the adult mouse of a complex of growth-controlling tissue-specific inhibitors is discussed, and evidence for its existence is reviewed.