Outer Dermis Research Articles

Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight

Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature. Post-flight samples showed significant up-regulation of genes related to inflammation and KRAS signaling across all skin regions. These spaceflight-associated changes mapped to specific cellular responses, including altered interferon responses, DNA damage, epithelial barrier disruptions, T-cell migration, and hindered regeneration were located primarily in outer tissue compartments. We also linked epithelial disruption to microbial shifts in skin swab and immune cell activity to PBMC single-cell data from the same crew and timepoints. Our findings present the inaugural collection and examination of astronaut skin, offering insights for future space missions and response countermeasures.

Chromatic leucism in the flap shell turtle, Lissemys punctata from Bangladesh

The spotted flap shell turtle, Lissemys punctata (Bonnaterre, 1789) has a distribution in Bangladesh, India, Myanmar, Nepal and Pakistan. In Bangladesh, this species is widely distributed throughout the freshwater wetlands and the low-lying floodplains, coastal islands, and hill districts. This species is listed in CITES (Appendix II) and protected by Bangladesh Wildlife Conservation & Security Act 2012 (Schedule II), where commercial trade is strictly prohibited. Lissemys punctata has an oval and domed carapace with olive-green colour spotted by dark yellow blotches. The head is also olive green often with yellow blotches, whereas the plastron is whitish or pale yellow. The colour of this species may vary depending on its habitat and defence strategy. Colour aberration in animals may occur due to a lack of melanin. Golden yellow colour aberration (chromatic leucism) is rare in animals, especially in turtles. This might be because of the absence of melanin in the outer dermis. The presence of high xanthophores and yellow pteridine pigments in the skin are also responsible for the golden yellow colour aberration.

Guide to Treatment of Tattoo Complications and Tattoo Removal.

Clinicians in the fields of general medicine, dermatology, and plastic surgery are in their work now and then confronted with tattoo complications. Recognizing the rather few important diagnostic groups and urgencies, the medical 'decision tree' of treatment becomes quite simple. Acute conditions are dominated by bacterial infections needing antibiotic treatment. Systemic infection is a matter of urgency and requires intravenous treatment in a hospital without delay to prevent septic shock. Inflammatory reactions are a real challenge. Chronic allergic reactions in red tattoos are mostly nonresponsive to topical corticoid and best treated with dermatome shaving with complete removal of the hapten concentrated in the outer dermis. Laser treatment of allergic reactions can boost the allergy with worsening and a potential risk of anaphylaxis and is thus not recommended in tattoo allergy. Chronic papulonodular reactions in black tattoos with pigment agglomeration can respond to local corticoid or be treated with dermatome shaving or lasers depending on availability. It is important to recognize sarcoidosis, which is strongly associated with reactions in black tattoos. Tattoo complications also include many rare but specific entities, which require individual treatment depending on the case and the disease mechanism. Removal of tattoos in individuals regretting their tattoo is performed using Q-switched nanosecond lasers and the recently introduced picosecond lasers. In view of the various tattoo pigments with different absorption spectra and the limited number of laser wavelengths, it is difficult to predict treatment outcome, and it is recommended to pretreat small test spots. Black and red colors are removed best, while other colors are difficult. Removal of large tattoos, especially when multicolored, is hardly achievable and not recommended. Clients often have unrealistic expectations, and informed consent and dialogue between the client and the laser surgeon before and during a treatment course is important since the client shall know the risk that removal can be unsuccessful, with complications and even disfiguring leading to regret at the end.

Herpes simplex virus type 2-infected dendritic cells produce TNF-α, which enhances CCR5 expression and stimulates HIV production from adjacent infected cells.

Prior HSV-2 infection enhances the acquisition of HIV-1 >3-fold. In genital herpes lesions, the superficial layers of stratified squamous epithelium are disrupted, allowing easier access of HIV-1 to Langerhans cells (LC) in the epidermis and perhaps even dendritic cells (DCs) in the outer dermis, as well as to lesion infiltrating activated T lymphocytes and macrophages. Therefore, we examined the effects of coinfection with HIV-1 and HSV-2 on monocyte-derived DCs (MDDC). With simultaneous coinfection, HSV-2 significantly stimulated HIV-1 DNA production 5-fold compared with HIV-1 infection alone. Because <1% of cells were dually infected, this was a field effect. Virus-stripped supernatants from HSV-2-infected MDDCs were shown to enhance HIV-1 infection, as measured by HIV-1-DNA and p24 Ag in MDDCs. Furthermore these supernatants markedly stimulated CCR5 expression on both MDDCs and LCs. TNF-α was by far the most prominent cytokine in the supernatant and also within HSV-2-infected MDDCs. HSV-2 infection of isolated immature epidermal LCs, but not keratinocytes, also produced TNF-α (and low levels of IFN-β). Neutralizing Ab to TNF-α and its receptor, TNF-R1, on MDDCs markedly inhibited the CCR5-stimulating effect of the supernatant. Therefore, these results suggest that HSV-2 infection of DCs in the skin during primary or recurrent genital herpes may enhance HIV-1 infection of adjacent DCs, thus contributing to acquisition of HIV-1 through herpetic lesions.

Introduction of dermatome shaving as first line treatment of chronic tattoo reactions

Background/aims: Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. Materials/methods: Fifty four tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed visually by the surgeon. Results: Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient’s severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12 months, respectively. Burden of operation was rated low. Patient satisfaction was high. Discussion/conclusion: Dermatome shaving is efficient and with few complications, and is proposed as first line treatment of chronic tattoo reactions. Shaving of such reactions apparently has been neglected during enthusiastic introduction of laser approaches, which in the treatment of allergic tattoo reactions may be relatively contra indicated and of special risk.

English

Contact dermatitis is an inflammatory response of the skin to an exogenous substance (irritant and/or allergen). It can be classified as follows: Irritant contact dermatitis, Allergic contact dermatitis, Photo contact, phototoxic dermatitis, Immediate contact reactions, Non-eczematous reactions Only the superficial regions of the skin are affected in contact dermatitis. Inflammation of the affected tissue is present in the epidermis and the outer dermis. 1 Unlike contact urticaria, in which a rash appears within minutes of exposure and fades away within minutes to hours, contact dermatitis takes days to appear. In our study we have shown the list of most common allergens found positive in our patients. STUDY DESIGN: It was a cross sectional study. METHOD: Study was conducted in mahatma Gandhi hospital Jaipur over a period of 4 months of duration. Patients suspected to have contact dermatitis were subjected to patch testing. Based on the history clinical signs and symptoms. Total 42 patients were short listed in 4 months of duration. RESULT: Our study showed that the most common allergen showing patch test positivity in both males and females were nickel sulphate, cophony, and cobalt sulphate. Patients showed significant improvement in their dermatitis after avoidance of the offending agent. CONCLUSION: Patch test is the method of choice and the gold standard in the detection of contact allergy and allergic contact dermatitis.

High‐frequency ultrasound imaging of tattoo reactions with histopathology as a comparative method. Introduction of preoperative ultrasound diagnostics as a guide to therapeutic intervention

Tattoo adverse reactions requiring diagnostic evaluation and treatment are becoming more common. The aim of this study was to assess tattoo reactions by 20-MHz ultrasonography referenced to histopathology as a comparative method. A total of 73 individuals with clinical adverse reactions in their tattoos were studied. Punch biopsies for reference histology were available from 58 patients. The Dermascan C(®) of Cortex Technology, Denmark, was employed. Total skin thickness and echo density of the echolucent band in the outer dermis were measured. Biopsy served for diagnosis and for determination of the level of cellular infiltration in the dermis. In every tattoo reaction studied, the skin affected was found thicker compared with regional control of the same individual (mean difference 0.73 mm). A prominent echolucent band of mean thickness 0.89 mm was demonstrated, primarily located in the very outer dermis but propagating to deeper dermal layers parallel to increasing severity of reactions. The thickness of the echolucent band correlated with the thickness of cellular infiltration determined by microscopic examination, R = 0.6412 (P < 0.001). Special diagnoses such as granulomatous and pseudolymphomatous tattoo reactions showed no distinct characteristics by ultrasound, but mainly displayed themselves by their advanced inflammatory component. It is demonstrated for the first time that ultrasound, with histopathology as the comparative method, can quantify the severity of tattoo reactions and non-invasively diagnose the depth of the inflammatory process in the dermis elicited by the microparticulate tattoo pigment, which itself is too minute to be imaged by ultrasound. Preoperative 20-MHz ultrasound scanning is introduced as a potentially useful method to guide therapeutic interventions by surgery and lasers.

The lateral pulley buried dermal suture

To achieve complete closure of wounds under tension, the lateral pulley buried dermal suture is described. The pulley loop exists not between the two margins of the wound, but in the outer dermis. The needle entry and exit occur on the undermined undersurface of the dermis. It has mechanical advantages similar to the modified buried dermal suture and compresses less marginal tissue. The pulley suture can secure the wound under tension without creating tension on the epidermis and superficial dermis at the wound edge.

In vivo imaging of intradermal tattoos by confocal scanning laser microscopy

In vivo confocal laser scanning microscopy (CLSM) is a new method for high-resolution imaging of intact skin in situ. Horizontal mapping of the outer skin is provided (magnification x 1000). Tattooing is popular all over the world; however, tattooed skin has not been studied in using CLSM. Tattoos in two volunteers were studied using the Vivascope1500 of Lucid Inc. Subepidermal massive deposits of dense, clustered pigment granules up to about 3 mum in size corresponding to black tattoos, and more scarce and diffuse deposits, corresponding to red, blue and green tattoos, were observed. Diffuse pigment granules tended to accumulate in the outer dermis underneath the level of the basement membrane zone. Dermal pigments from tattoos can be imaged in vivo using CLSM. This application of CLSM has an important future potential for pre-evaluation of tattoos before laser removal, predicting good or poor outcome of laser removal.

Fluorescence fibre‐optic confocal microscopy of skin in vivo: microscope and fluorophores

Fibre-optic confocal imaging in vivo is a new approach in the assessment of human skin. The objective is to describe a novel instrument and its operation and use in combination with fluorophores. The Stratum is a fibre-optic fluorescence confocal microscope especially developed for the study of skin and mucous membranes. The system is flexible and any body site can be studied with a hand-held scanner. The light source is a 488 nm argon ion laser. Horizontal (en face) images of the epidermis and outer dermis are produced with cellular resolution. Magnification is approximately 1000 x . Fluorescein sodium is routinely used as fluorophore (intradermal injection or application to the skin surface). This fluorophore is safe for human use in vivo, but other substances (rhodamine B, Acridine Orange, green fluorescent protein, curcumin) have also been studied. The instrument produces sharp images of epidermal cell layers from the epidermal surface to the sub-papillary dermis, with sub-cellular resolution. The scanner is flexible in use. The technique of intradermal fluorophore injection requires some skill. We consider this fibre-optic instrument a potentially important tool in skin research for non-invasive optical biopsy of primarily the epidermis. Present use is focussed on research applications, where the fluorophore distribution in the skin may illustrate morphological changes in the epidermis.

Study of three complementary techniques for measuring cutaneous hydration in vivo in human subjects: NMR spectroscopy, transient thermal transfer and corneometry - application to xerotic skin and cosmetics.

BACKGROUND/AIMS: The aim of this study was to determine the capability and the analytical quality of three different in vivo, non-invasive, quantitative methods for measuring skin hydration: two innovative methods that have been used for more than eight years - nuclear magnetic resonance spectroscopy (NMR-S) and transient thermal transfer (TTT) - and the more widely used and conventional corneometry. METHODS: The work presented evaluated the capability and precision, as well as cutaneous exploration depths, of the three methods. Experiments were carried out in vivo following the hydration, in kinetic terms, induced by topic application of reference moisturizing products. Spatio-temporal efficacy of a lipolotion was also studied by the TTT METHOD: Cases of xerotic skin were studied with TTT and corneometry. RESULTS: The results obtained showed better repeatability and reproducibility with the TTT and NMR-S methods than with corneometry. NMR-S is one of the only direct hydration measurement methods. It measures skin hydration down to the outer dermis with high precision. It is indicated for products having an action down to the deep cutaneous layers. By changing thermal power parameters, the TTT method can determine hydration to the outer, middle or deep epidermal layers. It is, therefore, possible to track the penetration of products in various layers of the epidermis. The small size of the probe enables the hydration measurement of skin sites (lips, eyelids) that were not, up to now, measurable with the two other methods. Corneometric investigations are restricted to the surface of the horny layer; measurements are easy and rapid but influenced by the composition of products applied to the skin and their phases: aqueous, oily or ionic. The xerotic skin study highlights the importance of exploration in different layers of the epidermis, as dehydration concerns not only the upper layers of the epidermis but also the medial and deep layers. With the TTT method, it has been possible to highlight the penetration dynamics of a lipolotion with, initially, an increase in the hydration in the outer epidermis, followed 3 h later by a transfer from the outer to the middle epidermis. CONCLUSION: NMR-S, TTT and corneometry represent three possible ways to assess skin hydration. Because they explore different cutaneous depths, they are more complementary than competitive. Transient thermal transfer, although a semi-direct method, is a precise, informative, and innovative solution to evaluate skin hydration at different epidermal depths and sites.

Cell-derived stiffening and plasticizing factors in sea cucumber (Cucumaria frondosa) dermis

The stiffness of holothurian dermis can be altered experimentally in vitro by changing the concentration of extracellular Ca(2+). Previous experiments with Cucumaria frondosa have established that these Ca(2+) effects are due to Ca(2+)-dependent cellular processes rather than to direct effects of Ca(2+) on the extracellular matrix. The present report describes two protein factors that are released from cells of C. frondosa dermis by membrane lysis and that directly alter the stiffness of the extracellular matrix. One factor, isolated from the inner dermis, increased tissue stiffness in the absence of Ca(2+). The second factor, from the outer dermis, decreased tissue stiffness in the presence of normal Ca(2+) levels. The relative abundance of these two factors in the inner and outer dermis suggests the possibility that the cells that control tissue stiffness are spatially segregated. Both factors were partially purified under non-denaturing conditions by anion-exchange and gel-filtration chromatography. The partially purified protein preparations retained biological activity. These results suggest that the stiffness of sea cucumber dermis is regulated by cell-mediated secretion of either the stiffening or plasticizing protein and that alterations in dermis stiffness brought about by manipulation of Ca(2+) levels are mediated by effects on secretion of one or both of these proteins.

Laser Deepithelialization of the Transverse Rectus Abdominis Musculocutaneous Flap

Total or partial skin deepithelialization of the transverse rectus abdominis musculocutaneous (TRAM) flap is an integral component of this technique for achieving a successful breast reconstruction. In a manner similar to dermabrasion, the carbon dioxide laser in a defocused mode permits precise removal by vaporization of the epidermis and outer dermis. The extended application of this method for deepithelializing the TRAM flap is simple, rapid, and safe. Because a portion of the dermis always remains intact, another inherent advantage of this method is preservation of the subdermal vascular plexus that may be important for maintaining any precarious flap perfusion.

The Chemical Peel

Chemical peeling of facial skin has become a valuable adjunct in the armamentarium of the facial aesthetic surgeon. Among the various techniques available, phenol solutions are the most commonly used. Peeling produces a controlled, partial-thickness chemical burn of the epidermis and the outer dermis. Several techniques are available to "fine tune" the depth of the peel. Regeneration of peeled skin results in a fresh, orderly, organized epidermis. In the dermis, a new 2- to 3-mm band of dense, compact, orderly collagen is formed between the epidermis and the underlying damaged dermis, which results in effective ablation of the fine wrinkles in the skin and a reduction of pigmentation. These clinical and histological changes are long lasting (15-20 years) and may be permanent in some patients. Because of the metabolism and systemic complications of phenol, patient selection should involve systemic evaluation of liver, renal, and cardiac function, as well as an evaluation of the skin quality and medication status of the patient. Because of potential cardiac arrhythmias, peeling must be performed in a medically supervised environment, with continuous cardiac monitoring. The local complications of peeling include pigmentation changes, scarring, milia, ectropion, infection, activation of herpes simplex, and toxic shock syndrome.

Skin elasticity in psoriasis. In vivo measurement of tensile distensibility, hysteresis and resilient distension with a new method. Comparison with skin thickness as measured with high-frequency ultrasound.

ABSTRACTThe skin elasticity of psoriasis plaques was measured in 10 patients suffering from psoriasis vulgaris with a recently introduced in vivo method with high reproducibility. The method is based on repeated applications of suction to a 0.79cm2 circular skin area, and measurement of tensile distensibility (TD), hysteresis (H) and resilient distension (RD) by the principle of electrical capacitance as calibrated with distance. Measurements of 23 plaques showed a decrease in TD and increases in H and RD when compared to regional control measurements. Experiments in 19 control regions with histamine skin‐pricks to evaluate the effects of cutaneous oedema on skin rheology showed that TD as well as H and RD became increased. The skin thickness of the plaques was increased by 68% as a mean, probably resulting from oedema of the outer dermis. The decreased TD, representing a component of stiffness, is probably related to a fixed zone of interdigitation between elongated and club‐shaped rete ridges and oedematous papillae while the increase in H and RD, representing a component of softness, is probably explained by the oedema of the outer dermis. Analyses of the relation between increase in thickness and rheology indicated that, in more advanced plaques, the skin may be in a state of mechanical locking with low hysteresis.