Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product.

The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in patients with DM. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. This study aimed to elucidate skin barrier impairment in patients with type 2 DM and its pathomechanisms using classic animal models of type 2 DM. Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between patients with type 2 DM and age- and sex-matched non-diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and biomolecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Patients with type 2 DM presented with epidermal barrier impairments, including SC hydration, which was influenced by blood glucose control (HbA1c level). In the lipid analysis of SC, ceramides, fatty acids and cholesterol were significantly decreased in patients with type 2 DM compared with controls. Type 2 DM murine models presented with severe hyperglycaemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal antimicrobial peptides (AMPs), an increase in receptors for advanced glycation end-product (AGE) in the epidermis and an increase in serum AGE. Impairment of the skin barrier was observed in type 2 DM, which results in part from a decrease in epidermal proliferation. Serum AGE and its epidermal receptors were increased in type 2 diabetic mice which display impaired skin barrier parameters such as epidermal lipid synthesis, LB production, epidermal AMP and SC lipids.

Periadnexal mucin as an additional histopathologic feature of chronic eczematous dermatitis.

BACKGROUND: Cutaneous mucinoses are a heterogeneous group of disorders characterized by an abnormal amount of mucin in the skin. However, the pathomechanism of an excessive mucin deposition in the skin is still unknown. Eczematous dermatitis is sub-classified histologically into acute, subacute, and chronic variants. The characteristic histopathologic findings for chronic eczema are variable. However, periadnexal mucin deposition is not known as a feature of chronic eczema. OBJECTIVE: To evaluate the presence of periadnexal mucin deposition in chronic eczematous dermatitis. METHODS: We analyzed the skin biopsy specimens from 36 patients who were pathologically diagnosed with chronic eczematous dermatitis. Alcian blue, colloidal iron, and periodic acid-Schiff stains were used to evaluate the mucin deposition in histologic sections. Two dermatologists and two dermatopathologists evaluated the degree of mucin deposition using a 4-point scale. RESULTS: Various amounts of mucin deposition were observed in the periadnexal area of patients who were diagnosed with chronic eczema. Mucin deposition was more visible after staining with mucin-specific stains. Evaluation of the staining analysis scores revealed that the staining intensities were significantly higher in patients with chronic eczema than age- and site-matched controls (normal, acute to subacute eczema, and psoriasis vulgaris). CONCLUSION: Periadnexal mucin (secondary mucinoses) may be an additional finding of chronic eczematous dermatitis.

Surveillance of home environment in children with atopic dermatitis: a questionnaire survey.

BACKGROUND: The increasing prevalence of atopic dermatitis (AD) suggests a role for environmental factors in triggering a genetic predisposition in sufferers. OBJECTIVE: The purpose of this study was to investigate home environmental factors related to AD severity. METHODS: We conducted a questionnaire survey about the home environmental factors in 380 children from two daycare centers and the Samsung Medical Center outpatient clinic. AD was diagnosed by Hanifin and Rajka's criteria and its severity was assessed by the Severity Scoring of Atopic Dermatitis index. Children were divided into normal control group, mild AD group and severe AD group. Home environmental factors were compared among the three groups and were statistically analyzed using analysis of variance, Chi-square test, Fisher's exact test, and multiple logistic analysis. RESULTS: Indoor remodeling activities, such as painting (p = 0.004), floor covering (p = 0.001) and wallpaper changing (p = 0.002) were associated with severity of AD. Those in the severe AD group were more likely to live in an apartment (p < 0.001). Severe AD was observed more frequently when the monthly income of household (p = 0.027) and final educational status of mother (p = 0.001) were higher. CONCLUSION: Some home environmental factors were associated with AD severity, but its causal relationship is not clear. Further research is needed to confirm these associations and to clarify whether they are causative.

Nevus sebaceous accompanying secondary neoplasms and unique histopathologic findings.

Nevus sebaceous (NS) is a type of classical nevus or congenital malformation that is often present at birth and commonly involves the scalp or face. The lesion usually presents as a linear, yellow, hairless, and verrucous plaque. It has been well-established that several benign and malignant tumors can develop from the NS; however, there have been no reports about ectopic fat cells in the dermis, and cornoid lamella arising from the NS. We report a case of NS on the scalp with accompanying unusual histopathologic findings.

Concurrent occurrence of mucocele and pyogenic granuloma.

A mucocele is a common, benign lesion of the oral cavity that develops following the extravasation or retention of mucous from a major or minor salivary gland. A pyogenic granuloma (PG) is also a common, benign condition characterized by proliferating capillaries that affect the skin and mucous membranes. The concurrent occurrence of a mucocele and a PG lesion has rarely been reported in the medical literature. This case study reports such a finding in a 16-year-old patient who presented to our department.

Case of epidermolysis bullosa with pyloric atresia.

Epidermolysis bullosa (EB) is a rare hereditary disorder characterized by formation of blisters following minor trauma. It has been traditionally categorized by the level of basement membrane zone separation into EB simplex (EBS), junctional EB (JEB), and dystrophic EB (DEB). Recently, hemidesmosomal EB has been proposed as a fourth category, which includes EB with muscular dystrophy and EB with pyloric atresia. We report here on a case of concomitant occurrence of EB and pyloric atresia, a rare form of EB.

A long-standing hyperglycaemic condition impairs skin barrier by accelerating skin ageing process.

Uncontrolled chronic hyperglycaemia including type 2 diabetes mellitus (DM) induces many skin problems related to chronic impaired skin barrier state. However, little is known about the skin barrier state of chronic hyperglycaemia patients, the dysfunction of which may be a major cause of their skin problems. In this study, we investigated whether a long-standing hyperglycaemic condition including type 2 DM impairs skin barrier homoeostasis in proportion to the duration and its pathomechanism. We utilized the Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of long-standing hyperglycaemia and Long-Evans Tokushima Otsuka rats as a control strain. We confirmed that a long-standing hyperglycaemia delayed skin barrier homoeostasis, which correlated with haemoglobin A1c levels. OLETF rats as a long-standing hyperglycaemia model exhibited decreased epidermal lipid synthesis and antimicrobial peptide expression with increasing age. Decreased epidermal lipid synthesis accounted for decreased lamellar body production. In addition, OLETF rats had significantly higher serum levels of advanced glycation end products (AGEs) and elevated levels of the receptor for AGE in the epidermis. A long-standing hyperglycaemic condition impairs skin barrier function including permeability and antimicrobial barriers by accelerating skin ageing process in proportion to the duration of hyperglycaemia, which could be a major pathophysiology underlying cutaneous complications of DM.

A Case of Atrophoderma of Pasini and Pierini Associated with Borrelia burgdorferi Infection Successfully Treated with Oral Doxycycline.

Atrophoderma of Pasini and Pierini is a form of dermal atrophy that manifests as either single or multiple, sharply demarcated, hyperpigmented, non-indurated patches. These patches are marked by a slight depression of the skin, with an abrupt edge (i.e., the "cliff-drop" borders), usually located on the backs of adolescents or young adults. The pathophysiology of the disease is unknown, but some authors have suggested a role of Borrelia burgdorferi infection. A 35-year-old woman visited our department because of asymptomatic, hypopigmented, depressed patches on her chest and back lasting for three months. Laboratory evaluations were normal, except for positive serum antibodies to Borrelia burgdorferi. Histologic examination revealed a significantly decreased thickness of the dermis. The patient underwent treatment with oral doxycycline 200 mg/day for six weeks, after which the depth of depression was improved. Herein, we report a case of atrophoderma of Pasini and Pierini, associated with Borrelia burgdorferi infection, successfully treated with oral doxycycline.

Anti-ageing effects of a new synthetic sphingolipid (K6EAA-L12) on aged murine skin.

Recently, we reported on the anti-ageing effects of K6PC-5. This compound induced keratinocyte differentiation and fibroblast proliferation by increasing sphingosine-1 phosphate synthesis. We performed this study to confirm the anti-ageing effects of new synthetic products (the K6EAA series) derived from K6PC-5 through an amino group induction. Cellular responses such as differentiation, proliferation and calcium mobilization were investigated using cultured human keratinocytes and fibroblasts. Also, we measured the expressions of collagen mRNA and protein using real time RT-PCR and ELISA, respectively. The K6EAA-L12 product, selected by in vitro screening, was evaluated for anti-ageing effects on intrinsically and extrinsically (photo) aged models of hairless mice. In the intrinsically aged murine skin, K6EAA-L12 showed anti-ageing effects by activating collagen synthesis, eventually causing dermal thickening. Also, in the photo-aged skin, the dermal collagen density and dermal thickness were increased. In photo-aged murine skin, K6EAA-L12 increased stratum corneum integrity by increasing corneodesmosome density and improved the barrier recovery rate. However, there were no changes in the expressions of epidermal differentiation maker proteins. In conclusion, topical K6EAA-L12, a new synthetic K6PC-5 derivative, improves intrinsically and extrinsically (photo) aged skin by increasing the collagen density and improving the skin barrier function.

Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study.

BACKGROUND: Dutasteride (Avodart) is a dual inhibitor of both type I and type II 5 alpha reductases, and thus inhibits conversion of testosterone to dihydrotestosterone, a key mediator of male pattern hair loss. OBJECTIVES: The aim of this randomized double-blind phase III study was to compare the efficacy, safety, and tolerability of dutasteride (0.5 mg) and placebo for 6 months of treatment in male patients with male pattern hair loss. METHODS: A total of 153 men, 18 to 49 years old, were randomized to receive 0.5 mg of dutasteride or placebo daily for 6 months. Efficacy was evaluated by the change of hair counts, subject assessment, and photographic assessment by investigators and panels. RESULTS: Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2) in dutasteride group and 4.7/cm(2) in placebo group and this difference was statistically significant (P = .0319). Dutasteride showed significantly higher efficacy than placebo group by subject self-assessment and by investigator and panel photographic assessment. There was no major difference in adverse events between two groups. LIMITATIONS: The study was limited to 6 months. CONCLUSIONS: This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss.

Cherry Angiomas on the Scalp.

Cherry angiomas are a common cutaneous vascular proliferation which manifests as single or multiple spots and occurs predominantly on the upper trunk and arms. They typically appear as round-to-oval, bright, red, dome-shaped papules and pinpoint macules measuring up to several millimeters in diameter. The histopathologic findings of a cherry angioma are consistent with a true capillary hemangioma, which is formed by numerous, newly developed capillaries with narrow lumens and prominent endothelial cells arranged in a lobular fashion in the papillary dermis. Herein, we report a case of multiple cherry angiomas on the scalp, an uncommon location for cherry angiomas.

[Standardized sweat chloride analysis for the diagnosis of cystic fibrosis in Korea].

BACKGROUND: Cystic fibrosis is a chronic progressive autosomal recessive disorder caused by the CFTR gene mutations. It is quite common in Caucasians, but very rare in Asians. Sweat chloride test is known to be a screening test for the cystic fibrosis due to the fact that electrolyte levels in sweat are elevated in patients. In this study, sweat chloride levels in Korean population were measured and analyzed by using standardized pilocarpine iontophoresis sweat chloride test. METHODS: The sweat chloride test was performed in 47 patients referred to Yondong Severance Hospital from August, 2001 to April, 2007 and 41 healthy volunteers. The sweat chloride tests were conducted according to the CLSI C34-A2 guideline using pilocarpine iontophoresis method, and the chloride concentrations in sweat were measured by mercurimetric titration. RESULTS: Four patients showed sweat chloride concentrations higher than 60 mmol/L. Reference interval was calculated as 1.4-44.5 mmol/L by analysis of the results of healthy volunteers (n=41). Four patients who exhibited high sweat chloride levels, had characteristic clinical features of cystic fibrosis and their diagnoses were confirmed either by repeated sweat chloride test or genetic analysis. CONCLUSIONS: Standardized sweat chloride test can be utilized as a useful diagnostic tool for cystic fibrosis in Koreans. In cases of sweat chloride levels higher than 40 mmol/L, the test should be repeated for the possible diagnosis of cystic fibrosis. All the confirmed Korean cases of cystic fibrosis showed sweat chloride level above 60 mmol/L.

K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin.

Sphingosine-1-phosphate (S1P), which is formed by phosphorylation of sphingosine through a process catalysed by sphingosine kinase (SK), is a multifunctional mediator of a variety of cellular responses including proliferation, differentiation, motility, and survival. K6PC-5, which was recently synthesized as a novel SK activator, is expected to increase S1P levels. Indeed studies have already demonstrated that K6PC-5 exhibits anti-aging effects on intrinsic aged murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and epidermal differentiation. However, photoaging and intrinsic aging have highly different clinical and histopathological properties. In this study, we developed a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC-5, as an SK activator, had anti-aging effects on photoaged murine skin in addition to its effects on intrinsic aged murine skin and determined the mechanism. K6PC-5 increased dermal collagen density in photoaged skin through increases in fibroblasts and collagen production. Photoaged murine skin treated with K6PC-5 showed an increase in stratum corneum (SC) integrity with increased corneodesmosome density and an improvement in barrier recovery rate. Matrix metalloproteinase 13 remained unchanged. These results indicate that topical application of K6PC-5 improves photoaged skin by improving skin barrier and increasing fibroblast count and function. In conclusion, K6PC-5, as an S1P activator, improves long-term UV-exposed aged skin as well as intrinsic aged skin.

Heparin-immobilized pluronic/PVA composite microparticles for the sustained delivery of ionic drug.

Heparin-immobilized Pluronic (F-68)/Polyvinylalcohol (PVA) composite microparticles were designed and characterized for the sustained drug delivery of ionic drug. Venlafaxine, antidepressant medication, was used as a model drug. For the efficient loading of ionic drug, heparin was immobilized into F-68/PVA composite microparticles. Differential scanning calorimetry (DSC) was used to understand the intra/intermolecular interactions in the heparin-immobilized F-68/PVA composite gels containing model drug. For the application as a sustained drug delivery system, the loading amount and release pattern of loaded drug were measured using high performance liquid chromatography (HPLC).

Hepatocyte transplantation for glycogen storage disease type Ib.

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia, caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib, caused by a deficiency of glucose-6-phosphate transporter (G6PT). We report that a substantial improvement was achieved following several infusions of hepatocytes in a patient with GSD-Ib. Hepatocytes were isolated from the unused cadaveric whole livers of two donors. At the first transplantation, approximately 2 x 10(9) cells (2% of the estimated recipient's total hepatocytes) were infused. Seven days later 1 x 10(9) (1% of liver mass) cryopreserved hepatocytes from the same donor were infused, and an additional 3 x 10(9) (3% of liver mass) cells from the second donor were infused 1 month after the second transplantation. After the hepatocyte transplantation, the patient showed no hypoglycemic symptoms despite the discontinuation of cornstarch meals. Liver biopsies on posttransplantation days 20 and 250 showed a normal level of glucose-6-phosphatase activity in presolubilization assay that was very low before transplantation. This was the first and successful clinical hepatocyte transplantation in Korea. In this study, hepatocyte transplantation allowed a normal diet in a patient with GSD-Ib, with substantial improvement in their quality of life. Hepatocyte transplantation might be an alternative to liver transplantation and dietary therapy in GSD-Ib.

The development of eosinophilic colitis after liver transplantation in children.

Tacrolimus-based immunosuppression in pediatric liver transplant recipients is known to be associated with EGID. Our goal was to determine the incidence, risk factors, and characteristics of EGID in our pediatric liver transplantation program. This study was a retrospective analysis of 38 pediatric liver transplant recipients. Rectal mucosal biopsy was performed to evaluate for gastrointestinal PTLD and eosinophilic colitis. There were 14 patients (37%) who were diagnosed with eosinophilic colitis. The mean age at transplantation was 10.8 +/- 1.8 months. Those with eosinophilic colitis had a higher incidence of peripheral eosinophilia (p = 0.003) during the first two months following transplantation and had a higher EBV infection rate. Symptoms, such as diarrhea, hematochezia, and abdominal pain, became apparent after an average of three months; diagnoses were made at 6.9 +/- 2.0 months after transplantation. There were eight patients (57%) with elevated food-specific IgE levels. With food restriction treatment, the symptoms of patients improved. EGID should be considered when clinical symptoms are present, because symptoms of this disorder are similar to those of gastrointestinal PTLD. It should also be considered when peripheral eosinophila is detected or when EBV seroconversion develops during the first two months following transplantation.

Efficacy of two triple eradication regimens in children with Helicobacter pylori infection.

Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen.