Effects of a moisturizer containing pseudo-ceramide and a eucalyptus extract on sweating function in adult atopic dermatitis: a double-blind, randomized, controlled left-right comparison clinical trial.

BACKGROUND: Many patients with atopic dermatitis (AD) have a decreased ability to sweat. Several factors can cause decreased perspiration, such as weak tight junctions of sweat ducts, reduced acetylcholine receptor function, and inhibition of perspiration by histamines. Parakeratosis of AD skin also decreases sweating by occluding sweat pores. Increased ceramide levels in the stratum corneum reduce parakeratosis by improving stratum corneum functions. Furthermore, ceramides and/or ceramide derivatives may affect claudin-3 and acetylcholine receptors. OBJECTIVE: In this study, we investigated the efficacy of a moisturizer containing pseudo-ceramide and a eucalyptus extract to increase ceramide levels in the epidermis to improve the sweating ability of patients with AD. METHODS: Nineteen patients with AD applied moisturizers with or without pseudo-ceramide and a eucalyptus extract on the cubital fossa of either arm twice a day for 4 weeks. Skin conditions and sweating ability, measured as the response to acetylcholine stimulation, were evaluated prior to the start of the study (Week 0) and at the end of Weeks 2 and 4. RESULTS: Both moisturizers improved the visually evaluated skin symptoms and skin hydration. However, only the moisturizer containing pseudo-ceramide and the eucalyptus extract significantly improved cutaneous barrier function and significantly increased the ceramide level in the stratum corneum. That moisturizer also increased the sweating volume and shortened the latency time for sweating, an indicator of sweating ability, but the other moisturizer did not. CONCLUSION: Based on these results, the moisturizer containing pseudo-ceramide and a eucalyptus extract helps recover the sweat function of AD patients.

Development of Topical Gel of Methotrexate Incorporated Ethosomes and Salicylic Acid for the Treatment of Psoriasis.

BACKGROUND: There is an unmet need for optimized drug delivery system of psoriasis therapy because of various issues like adverse reaction, permeation problem associated with convention treatment (oral and topical) available for psoriasis. OBJECTIVE: The goal was to develop an ethosomal gel of methotrexate (MTX)-incorporated ethosomes and salicylic acid (SA) and to evaluate and study its ethosomal gel potential in Imiquimod-induced psoriasis animal model to treat symptoms of psoriasis. METHODS: MTX-SA ethosomal gel was prepared by the cold method given by Touitou et al. and optimized by comparing it with MTX ethosomal gel and drug solution. Particle size, zeta potential, entrapment efficiency, and ex-vivo study were selected as the critical quality checking attributes. Psoriatic Area and Severity Index (PASI) score & histopathological examination were done for checking Antipsoriatic potential of MTX-SA ethosomal gel by using the imiquimod-induced psoriasis model. RESULTS: Optimized MTX-SA exhibited a particle size of 376.04 ± 3.47nm, EE(Entrapment efficiency) of 91.77 ± 0.02%. At the end of 24h, MTX-SA ethosomal gel exhibited a slow and prolonged release of MTX (26.13 ± 1.61% versus 6.97 ± 0.06%) compared to MTX drug solution. It also attributes of 43% retention study as compared to drug solution (13%). Besides, it essentially decreased the PASI score with the recuperation of normalcy of the mice's skin, while the MTX-SA gel displayed indications of gentle hyper and parakeratosis toward the completion of investigation when contrasted with the blank gel. CONCLUSION: The developed MTX-SA ethosomal gel formulation can be a promising alternative to existing MTX formulation in topically treating psoriasis.

Liquen nitidus sobre vitíligo: nueva variante del fenómeno de co-respuesta isotópica / Lichen nitidus arising on vitiligo: a new variant of the isotopic coresponse

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Localized parakeratotic hyperkeratosis in sixteen Boston terrier dogs.

BACKGROUND: Although zinc responsive dermatosis is typically a disorder of Arctic breed dogs, this study identifies similar cutaneous lesions on the face and pressure points of Boston terrier dogs. HYPOTHESIS/OBJECTIVES: To document the clinical and histological features of localized parakeratotic hyperkeratosis of Boston terrier dogs, to determine if the lesions respond to zinc supplementation and to determine whether tissue zinc levels were decreased in affected versus unaffected dogs. MATERIAL AND METHODS: Sixteen Boston terrier dogs with similar gross and histological findings were identified retrospectively from two institutions. Follow-up information for nine dogs from one institution was obtained from referring veterinarians using a questionnaire. Tissue zinc levels were measured from formalin-fixed paraffin-embedded skin biopsy samples of affected and unaffected dogs using inductively coupled plasma mass spectrometry. RESULTS: Mild to severe parakeratotic hyperkeratosis with follicular involvement was present in all 16 cases. Of the nine dogs for which follow-up information was available, five dogs received oral zinc supplementation and four dogs had documented clinical improvement or resolution of dermatological lesions. The median skin zinc levels were not significantly different between affected and unaffected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge this is the first report of localized parakeratotic hyperkeratosis in Boston terrier dogs, some of which improved with oral zinc supplementation. Prospective studies in Boston terrier dogs are warranted to document potential zinc deficiency (serum and/or tissue levels, pre- and post-treatment) and to objectively assess response to zinc supplementation and other therapies.

History of zinc in agriculture.

Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application.

Evaluation of histopathological changes in control biopsies which taken 48 sessions after NBUVB phototherapy for early-stage mycosis fungoides.

BACKGROUND: There are not many studies investigating histomorphological changes in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB) treatment. Our purpose is to evaluate histological features of phototherapy after 48 sessions and determine which parameters are more reliable for controlling skin biopsies. METHODS: Biopsies of 32 patients with early stage of MF, who were treated with NBUVB phototherapy, were histologically evaluated before and after the treatments, including epidermotropism, stratum corneum, epidermal thickness, dermal infiltration, papillary dermal fibrosis, vascular alterations, and other dermal changes. We discuss the histomorphological effects of NBUVB phototherapy on skin biopsies by comparing the responders with nonresponders, with before and after the treatment. RESULTS: 9 patients (28%) did not give any response to treatment. Alleviation in epidermotropism, increases in parakeratosis and normal keratosis, perivascular infiltration, and melanophages, decrease in the lichenoid/patchy lichenoid infiltration pattern after the treatment was statistically significant. Comparing by response, normalization of stratum corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells, the lichenoid/patchy lichenoid infiltration, the loss of inflammation were statistically significant in responders group. CONCLUSION: We detected a significant decrease in linearly arranged cells after phototherapy, indicating that it is an "important diagnostic parameter" in evaluation of therapeutic response.

Up-regulation of serpin SCCA1 is associated with epidermal barrier disruption.

BACKGROUND: Parakeratosis, the persistent presence of nuclei in the stratum corneum (SC) is associated with serious disruption of skin barrier function. Squamous cell carcinoma antigen 1 (SCCA1) is strongly up-regulated in inflamed and parakeratotic skin. OBJECTIVE: To find a biochemical marker for the SC barrier disruption, especially the disruption associated with parakeratosis. METHODS: An ELISA assay system was established to quantify SCCA1 in the extract of tape-stripped cornified cells. Transepidermal water loss (TEWL) and other skin parameters were measured and compared with the amount of SCCA1. Localization of SCCA1 was investigated immunohistochemically in various skin diseases with parakeratosis. Nuclei and SCCA1 on the skin surface were detected by staining of corniocytes collected on an adhesive-coated slide glass. RESULTS: SCCA1 showed strong up-regulation in lesional skin with psoriasis (466-fold), hayfever skin caused by Japanese ceder pollen (232-fold) and sun-exposed skin of healthy individuals (90-fold) compared to their normal sun-protected skin. The increased levels of SCCA1 were well correlated with increased values of TEWL and the number of parakeratotic cells in the SC. Furthermore, subjects with high levels of SCCA1 in the epidermis were more susceptible to barrier disruption by external stimuli, and this was accompanied with a further increase of SCCA1. We confirmed that localization of SCCA1 was limited to parakeratotic areas by using the skin surface staining technique. Immunohistochemical study also demonstrated that SCCA1 was always present at high levels in parakeratotic epidermis. CONCLUSION: All of our findings indicate that SCCA1 plays an important role in the induction of epidermal barrier disruption. SCCA1 may be a critical determinant of barrier function in the epidermis.

Necrolytic acral erythema without hepatitis C infection.

Necrolytic acral erythema is a newly described entity characterized by sharply demarcated scaly plaques on the dorsum of the hands and feet. More than 30 patients have been reported since 1996, all of whom had anti-hepatitis C virus antibody. A 32-year-old Taiwanese woman had been diagnosed with and treated for systemic lupus erythematosus with lupus nephritis about 10 years earlier. Soon thereafter, she noted several well-demarcated keratotic plaques with erythematous borders on her feet, with sparing of the soles. Histopathology showed diffuse parakeratosis with a neutrophil infiltrate, hypogranulosis, pale upper keratinocytes, scattered and grouped dyskeratotic cells, psoriasiform hyperplasia and a mild lymphocytic infiltrate in the upper dermis. The diagnosis was made after three biopsies. The lesions regularly worsened just before and during menstruation, but patch and intradermal tests for progesterone and estrogen were negative. There was no evidence of either hepatitis B or hepatitis C infection. The lesions did not respond to treatment with zinc. The rash regressed spontaneously when corticosteroids were stopped and recurred when they were restarted, finally resolving completely after she was treated with high-dose pulse steroids for her lupus.

Podophyllin reaction mimicking Bowen's disease in a patient with delusions of verrucosis.

A 40-year-old woman presented with a delusion of warts on the forehead, for which she was applying podophyllin toxin. A skin biopsy was taken, which showed prominent mitotic figures in the basal and suprabasal layers of the epidermis and apoptotic keratinocytes. Histopathologically Bowen's disease was suspected, but was discounted after clinicopathological correlation was obtained and showed absence of epidermal atypia or disorganization. This case demonstrates the histological resemblance of podophyllin reaction to Bowen's disease. Differentiation of self-inflicted from organic skin disease may be difficult, especially where histopathological findings are confounded by cutaneous application of toxins.

Incidental granular parakeratosis associated with molluscum contagiosum.

A patient presented with a 4-month history of slowly progressive pruritic papules on her trunk and extremities. Biopsies from 2 of these lesions revealed molluscum contagiosum. One of the biopsies also showed several small foci of granular parakeratosis. Based on the clinical features and course of this patient, the granular parakeratosis seems to be an incidental finding.

Citrus pulp for cattle.

Citrus pulp is classified as an energy concentrate by-product feed. Citrus by-products fed to beef cattle include citrus molasses, citrus meal, wet citrus pulp, dried citrus pulp, and pelleted citrus pulp; however, in current production systems, pulp (wet, dry, and pelleted) is the only by-product commonly used. Citrus pulp production in the United States is limited to specific subtropical regions, of which south central Florida remains the largest with additional production in California and Texas.

A Case of Pityriasis Rubra Pilaris in an Infant / 대한피부과학회지

Pityriasis rubra pilaris is a rare papulosquamous and keratotic disease. The orange hue to the erythema, the thickening of the palms and soles and so called 'islands of normal skin' contribute to establish the diagnosis based on morphologic features. We present a 6-month-old male patient with multiple scaly erythematous patches and 'island of normal skin' on the face. There is no palmoplantar keratoderma, nor onychopathy. Histopathologic findings revealed alternating parakeratosis and hypergranulosis in the epidermis and mild perivascular lymphocytic infiltration in the dermis. Unlike to Griffiths classification, he showed good responses to topical steroid and UV phototherapy.

Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters.

BACKGROUND: Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities. OBJECTIVES: Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity. PATIENTS AND METHODS: PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex(R), Bristol Myers Squibb, Princeton, NJ, U.S.A. ), a vitamin D3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects. RESULTS: PhK activity in units mg-1 protein was highest in active untreated psoriasis (1204 +/- 804.3; mean +/- SD), lower in the calcipotriol-treated group (550.7 +/- 192. 9), lower in curcumin-treated group (207.2 +/- 97.6), and lowest in normal skin (105.4 +/- 44.6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F3,36 = 48.79, P < 0.0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells. CONCLUSIONS: Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.

Modeling acne in vitro.

To help elucidate the factors responsible for the infundibular changes seen in acne, the human sebaceous pilosebaceous infundibulum was isolated by microdissection and maintained for 7 d in keratinocyte serum-free medium supplemented with 50 micrograms/ml bovine pituitary extract, 100 units/ml penicillin and streptomycin, 2.5 micrograms/ml amphotericin B and CaCl2(10H2O) to give a final Ca2+ concentration of 2 mM. Infundibular structure was maintained over 7 d in this medium; the pattern of cell division mimicked that in vivo. The rate of cell division was significantly higher than previously described for infundibula maintained in supplemented William's E medium, and moreover did not fall over 7 d. The addition of 1 ng/ml interleukin-1 alpha (IL-1 alpha) caused hypercornification of the infundibulum similar to that seen in comedones; this could be blocked by 1000 ng/ml interleukin-1 receptor antagonist (IL-1ra). In about 20% of subjects there was spontaneous hypercornification of the infundibulum that could be blocked by 1000 ng/ml IL-1ra, suggesting that the infundibulum is capable of synthesising IL-1 alpha. The addition of 5 ng/ml epidermal growth factor or 5 ng/ml transforming growth factor-alpha to the medium caused a disorganisation of the keratinocytes of the infundibulum that resulted in rupturing similar to that seen in the more severe, purulent grades of acne. The addition of 1 microM 13-cis retinoic acid caused a significant reduction in the rate of DNA synthesis and apparent parakeratosis. We are now, therefore, able to model histologically the major infundibular changes in acne.

Cutaneous Horn Originated from Condyloma Acuminata / 대한피부과학회지

We report a case of cutaneous horn originated frorn condyloma acuminata in a 25 year-old man. The patient showed yellowish brown hyperkeratotic masses on the prepuce, coronal sulcus and multiple asymptomatic pinkish cauliflower-like projections in both inguinal folds and perianal area. Skin biopsies were taken from the base of the penile lesions andinguinal, perianal area exhibited marked hyperkeratosis and parakeratosis in addition to the typical findings of condylorna acuminaturn. In situ hybridization technique for Human papilloma virus(HPV) showed positive reaction to HPV 11. All lesions were removed by surgical excision, electrocauterization and podophyllin application, but condyloma acuminatum recurred several times thereafter.

Dietary fibre in the diet of the growing pig: effects on apparent digestibility and resultant implications for its use in reducing the incidence of oesophagogastric parakeratosis.

The effects on apparent digestibility of increasing dietary fibre concentrations in barley-based diets by substituting for barley either bran, oatmeal by-product, guar gum or pectin were studied using 72 pigs. Increasing substitutions of bran up to a maximum of 300 g kg-1 gave progressive decreases in apparent digestibility of dry matter, ether extract and gross energy fractions and in digestible and metabolisable energy contents, progressive increases in apparent digestibility of modified acid detergent fibre but had no consistent effect on either nitrogen or extract free of nitrogen fractions. Increasing substitution of oatmeal by-product up to the same maximum gave significant linear decreases in apparent digestibility of dry matter, extract free of nitrogen and gross energy, significant depressions in apparent digestibility of modified acid detergent fibre and significant increases in ether extract. Guar gum and pectin, both substituted to a maximum of 50 g kg-1 had no significant effects on apparent digestibility. The results are discussed in the context of the concentrations of dietary fibre needed to reduce the incidence of oesophagogastric parakeratosis.

Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency.

A patient with neonatal citrullinemia (argininosuccinic acid synthetase deficiency), a heritable disorder of the urea cycle, developed a generalized cutaneous eruption at 35 days of age. The skin lesions consisted of erosive, erythematous, scaling patches and plaques. The plasma arginine concentration at that time was low. After treatment with oral arginine supplements, the cutaneous lesions rapidly resolved and the plasma arginine concentration normalized. Histologic features of pretreated lesions included parakeratosis, crust formation, absence of a granular cell layer, pallor of the upper epidermal cells, and a mild, superficial, perivascular, mononuclear-cell infiltrate. Since the patient's skin lesions responded to arginine supplements, and since arginine is a component of keratin, we postulate that the skin lesions are the result of arginine deficiency.

[Exogenous zinc deficiency syndrome]. / Das exogen bedingte Zinkmangelsyndrom.

Two cases of acquired zinc deficiency after excessive bowel resection and total pancreatectomy and after total parenteral nutrition are reported. Skin lesions include diffuse hair loss and a psoriasis like dermatitis localized mainly at acral areas and around body orifices, which disappeared rapidly after oral supplementation of zinc sulfate. Clinical symptoms, etiological factors, differential diagnosis and therapy are discussed.

Scale prophylaxis. A new antiparakeratotic assay.

This article describes a new animal model for the evaluation of drugs that may prevent the development of parakeratosis. The advantages of this model are simplicity, economy, and the opportunity to observe the possible occurrence of acute systemic toxic reactions. High-boiling coal tar acids (phenols), vitamin A (retinyl acetate), and hydrocortisone butyrate (Locoid) were assayed. Only tar phenols consistently prevented scale development. Vitamin A was not properly screened because of toxic effects that resulted in premature termination of the experiment.

Photochemotherapy for Psoriasis / 대한피부과학회지

The beneficial effects of sunlight and ultraviolet light for the treatment, of psoriasis vulgaris has long been recognized. Parrish et al were the first to introduce a controlled light source, which allowed the delivery of a known quantity of light energy to the patients skin after the patient had ingested a photosensitizer, 8-methoxypsoralen (methoxsalen) two hours previous to UVA exposure. This successful treatment has become known as PUVA (psoralen and UVA). PUVA photochernotherapy denotes a systemic approach that is based on the interaction of light and a photoactive drug. Parrish et al have described successful treatment of psoriasis with PUVA and other investigators alI over the world have confirmed their beneficial results. The rationale of photochemotherapy in psoriasis is the inhibition of the increased DNA synthesis within the psoriatic lesions by the interaction of psoralen molecule and light energy in the UVA range(320-400nm). The present study was undertaken to evaluate the therapeutic effectiveness of PUVA photochernotherapy combining orally administered methoxsalen and UAA exposure using Dermatron UVA phototherapy system in patients with wi5espread psoriasis. A total of 15 patients with psoriasis over more than 30% of their bodies were selected at the department of dermatology, National Medical Center through March 1978 to September 1978. Oral administration of methoxsalen, 20 to 50 mg doses according to body weight, was followed by exposure to a high-intensity longwave ultraviolet light emitting a continuous spectrum between 320 and 400nm (peak emission, 350 - 365nm). Initial UVA exposure times were based on each patients minimal phototoxicity dose (MPD) and exposure times were increased at each treatment by 1 - 2 minutes to maintain minimal erythema. Frequency of treatment was two to three times weekly. Once the psoriatic lesions had, cleared completely the patient was placed on a maintenance schedule. If psoriasis recurred the frequency of treatment was increased. The results were as follows: l. 5 patients were dropped out due to unknown reasons. 2. 7 cases showed clearing of over 95, of the lesions (Response 5'). Mean number of PU VA therapy was 16. 7. During 1 4 months follow-up period, 4 cases remained free of psoriasis but 3 cases couldn't be followed. 3. Immediate side effects of PUVA were temporary and generally mild. No significant changes in laboratory screenings were noted. Side effects of therapy included transient nausea(33.3%), dizziness(26.7%), erythema.(66.7%), pruritus (60%), increased pigrnentation(100 %). 4. Comparison of pre-and post-PUVA therapy in biopsy specimens by light microscopy revealed histologic improvement evidenced by diminished acanthosis and parakeratosis, and regeneration of granular layers in all of 8 cases. Glycogen accumulation in the affected epiderrnis was significantly decreased or absent after PUVA therapy in all cases.