Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation, pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens, and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD.
Anti-Infective Agents/pharmacology ; Dermatitis, Atopic/*enzymology ; Endopeptidases/metabolism ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Inflammation ; Models, Biological ; Models, Genetic ; Peptide Hydrolases/*metabolism ; Receptor, PAR-2/*metabolism ; Serine Proteases/metabolism ; Signal Transduction ; Skin/enzymology/pathology ; Treatment Outcome

Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.
*Skin Physiology ; Skin Diseases/*metabolism/physiopathology ; Skin/*metabolism ; Permeability ; Humans ; Animals

Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.
*Skin Physiology ; Skin Diseases/*metabolism/physiopathology ; Skin/*metabolism ; Permeability ; Humans ; Animals

BACKGROUND: Several studies have been performed to evaluate the efficacy of dietary n-3 fatty acid for patients with renal dysfunction. While about 40% to 80% of patients with end-stage renal disease (ESRD) complain about pruritus and xerosis, there are few reports on the effects of topical n-3 fatty acid on these symptoms. OBJECTIVE: In order to investigate the possible beneficial effects of topical n-3 fatty acid, oils extracted from chia (Salvia hispanica) seed were formulated into topical products, the effects of which were measured. METHODS: Five healthy volunteers having xerotic pruritus symptoms and 5 patients with pruritus caused by either ESRD or diabetes were involved in this study. A topical formulation containing 4% chia seed oils were applied for an 8-week duration. Subjective itching symptoms were assessed on a 6-point scale, as were other skin functions, namely transepidermal water loss and skin capacitance. RESULTS: After the 8 weeks of application, significant improvements in skin hydration, lichen simplex chronicus, and prurigo nodularis were observed in all patients. A similar improvement was also observed among healthy volunteers with xerotic pruritus. Improvement of epidermal permeability barrier function and skin hydration, represented by trans-epidermal water loss and skin capacitance, respectively, were also observed. No adverse effects were observed in all the tested patients and volunteers. CONCLUSION: Chia seed oil can be used as an adjuvant moisturizing agent for pruritic skin, including that of ESRD patients.
alpha-Linolenic Acid ; Fatty Acids, Omega-3 ; Humans ; Kidney Failure, Chronic ; Methylmethacrylates ; Neurodermatitis ; Oils ; Permeability ; Polystyrenes ; Prurigo ; Pruritus ; Seeds ; Skin ; Water Loss, Insensible

BACKGROUND: Although the topical application of glycolic acid (GA) could possibly exert some effects on the normal epidermal permeability function, the exact effects and its mechanism of action have not been well documented. OBJECTIVE: This study was conducted to investigate the effects of GA on the expression of epidermal cytokines and to clarify its chelation effect on the epidermal calcium ions, which are known to control the secretion of lamellar bodies. METHODS: After topical application of 70% GA aqueous solution on the flank of hairless mice, the expression of epidermal IL-1alpha and TNF-alpha was assessed and the change of epidermal calcium ions was evaluated. RESULTS: The results could be summarized as the following: (1) real time reverse transcriptase polymerase chain reaction and immunohistochemical staining studies showed increases in mRNA and protein expression of epidermal IL-1alpha and TNF-alpha; (2) the GA reduced intracellular calcium ion concentrations in vitro and resulted in the loss of epidermal calcium gradient in vivo. CONCLUSION: These results suggest that, like iontophoresis or sonophoresis, GA could influence the skin's barrier homeostasis, possibly by lowering the epidermal calcium ions.
Animals ; Calcium* ; Cytokines* ; Homeostasis ; Ions ; Iontophoresis ; Mice ; Mice, Hairless* ; Permeability ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger ; Tumor Necrosis Factor-alpha

PURPOSE: Various therapeutic approaches have been suggested for preventing or reducing the adverse effects of topical glucocorticoids, including skin barrier impairment. Previously, we have shown that impairment of skin barrier function by the highest potency topical glucocorticoid, clobetasol 17-propinate (CP), can be partially prevented by co-application of a physiological lipid mixture containing pseudoceramide, free fatty acids, and cholesterol (multi-lamellar emulsion [MLE]). Skin atrophic effects of CP were also partially reduced by MLE. In this study, the preventive effects of MLE on the lowest potency topical glucocorticoid, hydrocortisone (HC), were investigated using animal models. METHODS: Anti-inflammatory activity of topical HC was evaluated using a 12-O-tetradecanoylphobol-13-acetate-induced skin edema model. Topical steroid induced adverse effects were evaluated using hairless mouse. RESULTS: The results showed that the anti-inflammatory activity was not altered by co-application of either MLE or hydrobase. However, co-application of MLE and 1.0% HC showed less impairment in the epidermal permeability barrier function, skin hydration, and skin surface pH compared with hydrobase. Stratum corneum integrity, evaluated by measuring trans-epidermal water loss after repeated tape stripping, showed less damage with MLE co-application. Long-term application of topical HC induced skin atrophy, measured by a reduction in skinfold and epidermal thickness and in the number of epidermal proliferating cell nucleus antigen (PCNA)-positive keratinocytes. Co-application of MLE did not affect the skinfold or epidermal thickness, but the number of PCNA-positive keratinocytes was less decreased with MLE use. CONCLUSIONS: These results suggest that co-application of MLE is effective in reducing the local adverse effects of low-potency topical glucocorticoids and supports the therapeutic efficacy of physiological lipid mixtures on skin barrier function.
Animals ; Atrophy ; Cell Nucleus ; Cholesterol ; Clobetasol ; Edema ; Fatty Acids, Nonesterified ; Glucocorticoids ; Hydrocortisone ; Hydrogen-Ion Concentration ; Keratinocytes ; Permeability ; Skin ; Steroids ; Water Loss, Insensible

Cerebral autoregulation is the mainternance of a constant cerebral blood flow over a wide range of cerebral perfusion pressure. But irreversible hypoxic brain damage may occur as a consequence of such diverse conditions as lung and heart disease, shock, seizure or an episode of severe hypotension, and is potential hazard to any patient undergoing general anesthesia. The ultimate degree of neurological recovery may range from brain death and vegetative state to minor psychiatric disturbance and even normality, and is determined by the severity of the initial stress and wheather or not adequate resuscitation was commenced before irreversible brain damage. We performed an experiment to determine the protective effect of the calcium channel blocker nimodipine on the neuronal injury following cerebral ischemia in a rat model. The result were as follows: 1) Mean arterial pressure decreased more significantly in the nimodipine-treated group than the saline-treated group (p<0.01). 2) With respect to the degree of neuronal damage following cerebral ischemia, it decreased more significantly in the nimodipine-treated group than the saline-treated group (p<0.01).
Anesthesia, General ; Arterial Pressure ; Brain ; Brain Death ; Brain Ischemia* ; Calcium Channels ; Heart Diseases ; Homeostasis ; Humans ; Hypotension ; Hypoxia, Brain ; Lung ; Models, Animal ; Neurons* ; Nimodipine* ; Perfusion ; Persistent Vegetative State ; Resuscitation ; Seizures ; Shock

BACKGROUND: Among the various methods for chemical peeling, it is possible to select a wide range of peeling agents for particular patients. OBJECTIVES: The objective of present study was to investigate the effects of various chemical peeling agents on the epidermal permeability barrier of hairless mice skin and to clarify the histologic alteration in epidermal structure, thus to apply in the clinical practices. METHODS: We have applied 35% and 70% glycolic acid (GA) aqueous solutions, 30% of salicylic acid (SA) solution of PEG400, Jessner's solution and 15%, 30% and 50% of trichloroacetic acid (TCA) aqueous solution to the flank of hairless mice. TEWL (trans-epidermal water loss) values were measured before and immediately after the application and 3, 6, 12 and 24 hours following treatment. Biopsy specimens were evaluated with light and electron microscopy for epidermal structural changes. RESULTS: There were no significant changes in TEWL for the GA and SA solution treated skin, regardless of their concentration. For the TCA and Jessner's solution, TEWL increased immediately after treatment and recovered the basal levels about 90% after 24 hours for Jessner's solution and low concentrated TCA solution, but did not recovered for high concentrated TCA solution. On light and electron microscopic examination, exfoliating effect was seen in every case and as for SA and Jessner's solution treated skin, keratolysis at hair follicles was also seen. Slight epidermal necrosis was seen in every case, except in GA treated skin. CONCLUSION: The present results suggest that using topical agents such as glycolic acid can induce the change in the architecture of the epidermis without disrupting the skin barrier.
Animals ; Biopsy ; Epidermis ; Hair Follicle ; Humans ; Mice ; Mice, Hairless ; Microscopy, Electron ; Necrosis ; Permeability ; Salicylic Acid ; Skin* ; Trichloroacetic Acid

Herein is a review of eigthy six surgical cases from March to August, 1986 with recieved tetracaine hrdrochloride spinal anesthesia. In an attempt to relieve postoperative pain, 0.5 mg morphine sulfate was administrated into the lumbar Subarachnoid space. Pruritus, a side effect of intraSpinal morphine, was explored in detail. The results were as follows : 1) The incidence of Pruritus was 67.4%, 65.5% in man find 71.0% in Woman. 2) The time of onset of pruritus was between 30 and 120 minutes with an average of 79.1 minutes. 3) Pruritus primary occurred on the face(87.9%). especially on the nasal, perinasal and periocular areas. Other sites included the scalp, neck, chest, abdomen, shoulder, hip, thigh, flank, and whole body. 4) The severity of pruritus was classified as mild and moderate, but 4 cases(6.9%) were regarded as severe and were treated with naloxone. 5) The duratiun of pruritus was from 15 minutes to 19 hours with an average of 4.7 hours. 6) There was no significant difference in the prevention of pruritus between the group recieving diphenhydramine and the one which received normal saline.
Abdomen ; Anesthesia, Spinal ; Diphenhydramine ; Female ; Hip ; Humans ; Incidence ; Morphine* ; Naloxone ; Neck ; Pain, Postoperative ; Pruritus* ; Scalp ; Shoulder ; Subarachnoid Space ; Tetracaine ; Thigh ; Thorax

BACKGROUND: Disturbed keratinization of the follicular infundibulum is the earliest change in comedo formation. The relative decrease in linoleic acid in the sebum could be responsible, in part, for this abnormal keratinization. OBJECTIVE: This study was conducted to evaluate the effects of topically applied multi-lamellar emulsion containing linoleic acid (MLE/LA) on experimentally induced comedones. METHODS: To induce comedo formation, 50% oleic acid (OL) in macrogol 400 was applied to the ventral surface of both ears of New Zealand white rabbits. Twenty ears of ten rabbits were randomly divided into four treatment groups (5 ears in each group). Four groups (OL only, OL and MLE/LA, OL and MLE, OL and control vehicle containing LA) were treated twice daily for 2 weeks. The relative increase in areas of the comedo was evaluated by digital image analysis. The morphologic changes around the epithelial lining of the comedo were observed by light microscopy and scanning electron microscopy. RESULTS: After 2 weeks of application, only the OL and MLE/LA combined treated group showed significantly less (by 1.23-fold, p<0.05) increase in comedo size when compared to the OL treated group (by 1.86-fold). Upon light microscopy and scanning electron microscopy examination, the MLE/LA treated ears showed a lesser degree of epidermal hyperplasia and hyperkeratosis in the follicular infundibulum compared with the OL treated ears. CONCLUSION: Topical MLE/LA might have an inhibitory effect on the formation of OL induced comedones.
Ear ; Hyperplasia ; Linoleic Acid* ; Microscopy ; Microscopy, Electron, Scanning ; Oleic Acid ; Polyethylene Glycols ; Rabbits ; Sebum