Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease that affects a large number of children and adults in Korea. The treatment of AD requires a comprehensive approach that includes evaluation of potential triggers and education of the patients and family members regarding proper avoidance measures. Because existing remedies for AD do not cure the disorder itself, a program of disease control and management should be pursued. Topical corticosteroids are the effective and relatively safe therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects. The topical calcineurin inhibitors such as pimecrolimus and tacrolimus allow a steroid-free, anti-inflammatory topical therapy of AD. Occasionally, however, children afflicted with severe AD require more intensive therapies (e.g., ultraviolet light exposure systemic corticosteroids, and cyclosporine) that need close monitoring. This review focuses on the current guidelines of managing AD regarding the efficacy and safety of several pharmacologic options. Management strategies discussed include topical corticosteroids, topical calcineurin inhibitors, antihistamines and anti-infectives. A management algorithm is also presented.
Adrenal Cortex Hormones ; Adult ; Atrophy ; Calcineurin ; Child ; Dermatitis, Atopic* ; Education ; Histamine Antagonists ; Humans ; Korea ; Skin ; Skin Diseases ; Tacrolimus ; Ultraviolet Rays

Animals ; Calcineurin ; metabolism ; Diet, High-Fat ; Dietary Fats ; administration & dosage ; Male ; Myocardium ; metabolism ; Physical Conditioning, Animal ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxides ; antagonists & inhibitors

Two intracellular signal pathways mediated by cAMP and protein kinase C (PKC) were involved in the regulation of FN gene expression (Lee et al., Exp. Mol. Med. 30: 240, 1998). In this study, a possible involvement of protein phosphatase-dependent pathways in the regulation of FN gene expression was investigated by using protein phosphatase type 2B (PP2B) inhibitors, cyclosporin A and ascomycin. Both cyclosporin A and ascomycin increased the levels of FN mRNA in WI-38 human lung fibroblasts and the SV40-transformed WI-38 cells but not in MC3T3-E1 osteoblasts. The expression of FN appears to increase from six hours up to 48 hours after treatment suggesting that it is not an immediate effect. In addition, this effect required a new protein synthesis. Neither cyclosporin A nor ascomycin affects the phorbol myristate acetate (PMA)-induced stimulation of FN gene expression and the same result occurred in vice versa suggesting the mechanism of PMA and cyclosporin A/ascomycin in the regulation of FN gene expression may share a common downstream pathway. Taken together, this study suggests that PP2B is involved in the regulation of FN gene expression in normal and transformed fibroblasts but not in osteoblasts.
Animal ; Calcineurin/antagonists & inhibitors* ; Cell Line, Transformed ; Cell Transformation, Viral ; Cyclosporine/pharmacology* ; Enzyme Inhibitors/pharmacology ; Fibroblasts ; Fibronectins/metabolism ; Fibronectins/genetics* ; Gene Expression Regulation* ; Human ; Lung/cytology ; Mice ; Osteoblasts ; Tacrolimus/pharmacology ; Tacrolimus/analogs & derivatives*

Calcineurin Inhibitors (CNIs) and Corticosteroids have been the main immunosuppressive agents in solid organ transplantation. Many studies have confirmed the positive impacts of withdrawal/avoidance of these agents, separately, on their side effect profiles. A pilot study was performed avoiding both agents among low-immunological-risk living donor kidney transplant recipients at a single center. Seventeen recipients were maintained on the double avoidance protocol during the study period beginning July 2002 through December 2003. Three rejection episodes occurred (out of ten) among related donor kidney recipients and six episodes (out of seven) among unrelated donor kidney recipients. Although most of the rejections were reversed with a short course of corticosteroids, the protocol was revised to exclude the unrelated donor kidney recipients. There were higher incidences of wound complications among recipients who received the initial loading dose of Sirolimus. Double avoidance of CNIs and corticosteroids is possible in living donor kidney transplant recipients with an acceptable incidence of rejection. Proper management of the side effects of Sirolimus could further minimize the incidence of rejection. A multi-center randomized study is recommended in order to recognize the benefits of avoiding CNIs and corticosteroids in renal transplant recipients.
Adrenal Cortex Hormones ; Adult ; Aged ; Antibodies, Monoclonal/*therapeutic use ; Calcineurin/antagonists & inhibitors ; Chimeric Proteins/*therapeutic use ; Drug Therapy, Combination ; Enzyme Inhibitors ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Kidney Transplantation ; *Living Donors ; Male ; Methylprednisolone/*therapeutic use ; Middle Aged ; Mycophenolic Acid/*analogs & derivatives/*therapeutic use ; Pilot Projects ; Sirolimus/*therapeutic use

Down syndrome critical region 1 (DSCR1), an oxidative stress-response gene, interacts with calcineurin and represses its phosphatase activity. Recently it was shown that hydrogen peroxide inactivates calcineurin by proteolytic cleavage. Based on these facts, we investigated whether oxidative stress affects DSCR1-mediated inactivation of calcineurin. We determined that overexpression of DSCR1 leads to increased proteolytic cleavage of calcineurin. Convertsely, knockdown of DSCR1 abolished calcineurin cleavage upon treatment with hydrogen peroxide. The PXIIXT motif in the COOH-terminus of DSCR1 is responsible for both binding and cleavage of calcineurin. The knockdown of overexpressed DSCR1 in DS fibroblast cells also abrogated calcineurin proteolysis by hydrogen peroxide. These results suggest that DSCR1 has the ability to inactivate calcineurin by inducing proteolytic cleavage of calcineurin upon oxidative stress.
Adenoviridae/genetics ; Adult ; Animals ; Calcineurin/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Chromatin Immunoprecipitation ; Down Syndrome/*metabolism/pathology ; Fibroblasts/metabolism/pathology ; Humans ; Hydrogen Peroxide/pharmacology ; Immunoglobulin G/immunology ; Intracellular Signaling Peptides and Proteins/*physiology ; Male ; Mice ; Mice, Inbred ICR ; Muscle Proteins/*physiology ; Neuroblastoma/genetics/metabolism/pathology ; Neurons/cytology/metabolism ; Oxidants/pharmacology ; Oxidative Stress ; Peptide Fragments/immunology ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/pharmacology ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction ; Skin/pathology ; Young Adult