Comparative study of skin autofluorescence expression in atopic dermatitis and psoriasis: A prospective in vivo study.

BACKGROUND/PURPOSE: Treatment of atopic dermatitis (AD) and psoriasis requires their differentiation from other eczematoid dermatitis and a determination of disease severity. However, both can be clinically difficult and the findings subjectively interpreted. We investigated the utility of in vivo autofluorescence (AF) measurements for diagnosis of both diseases, and determination of severity. MATERIALS AND METHODS: Thirty patients with AD and 30 with psoriasis were recruited, together with sex- and age-matched patients with healthy skin. AF intensity was measured using the EcoSkin® fluorescence video dermatoscope. In AD and psoriasis patients, AF in non-sun-exposed lesional and non-lesional skin was measured. To identify the locations that reflect characteristics of AD, AF was also measured at the other sites in the patients with AD. RESULTS: AD was associated with lower AF and psoriasis with higher AF intensity peaking around 620 nm. In addition, skin AF intensity of each disease was associated with severity of lesion. CONCLUSIONS: Non-invasive measurement of skin AF in vivo can aid in diagnosis of AD and psoriasis as well as in treatment monitoring.

Pilot study on the correlation between skin auto-fluorescence and serum antioxidant enzyme: skin auto-fluorescence is negatively associated with levels of malondialdehyde.

BACKGROUND/PURPOSE: Various methods have been used to objectively record skin changes. However, estimating the intrinsic and extrinsic aging of skin remains a challenge. Our objective was to study intrinsic skin aging with respect to patient age and extrinsic photo-aging of human dorsal (photo-exposed) and volar (photo-protected) forearm in vivo through skin auto-fluorescence (AF). We also examined the correlations between serum antioxidant enzyme, malondialdehyde(MDA), and skin AF. METHODS: 37 healthy volunteers were enrolled. We measured skin AF and its heterogeneity on the dorsal and volar forearms. We also examined serum concentration of catalase, superoxide dismutase, vitamin E, and MDA levels in every participant. RESULTS: In photo-protected areas, skin AF intensity in the 40 years or older group was significantly higher compared to the group less than 40 years-old. On the other hand, heterogeneity value was significantly higher in the less than 40 years-old group in photo-protected area. With respect to serum antioxidant enzyme and MDA level, only MDA level showed a negative correlation with skin AF intensity in photo-exposed area. CONCLUSION: We determined that skin AF intensity of the photo-protected area reflects intrinsic skin aging. In addition, degree of photo-aging could be indirectly inferred by skin AF of photo-exposed area and serum MDA level.

Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

BACKGROUND: Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. AIM: To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. METHODS: Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. RESULTS: There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). CONCLUSIONS: The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV.

Impact of chemical peeling combined with negative pressure on human skin.

OBJECTIVE: In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. METHODS: Thirteen female subjects (average age: 29.54 ± 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. RESULTS: The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P < 0.05). The TEWL and skin blood flow recovered to baseline after 2 days, and TEWL was significantly decreased at 7 days compared with chemical peeling alone (P < 0.05). CONCLUSIONS: Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier.

Effect of mycophenolic acid on proliferation of dermal papilla cells and induction of anagen hair follicles.

BACKGROUND: Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, has anti-inflammatory effects, and is widely used as an immunomodulatory agent. However, the beneficial effect of MPA in hair-loss disorders is not fully understood. AIM: To investigate the direct effect of MPA on dermal papilla cells (DPCs), and to examine the hair growth-stimulating effects of MPA topically applied to mouse skin. METHODS: Cultured DPCs were treated with various concentrations of MPA and analysed by MTT assay. Expressions of hair growth-related genes, including Wnt/ß-catenin pathway-related genes and cellular apoptosis-regulating genes, such as Bcl-2, Bax and caspase-9, were examined using reverse transcription (RT)-PCR and western blotting. The Wnt/extracellular signal-regulated kinase (ERK) pathway was analysed by western blotting. The effect of topically applied MPA on anagen hair follicle induction after microneedle (MN) treatment with or without minoxidil (MXD) was evaluated by histopathological examination and RT-PCR. RESULTS: MPA showed a promoting effect on DPC proliferation, which was associated with increased Axin2 transcription levels. In addition, phospho-ERK protein was detected in the MPA-treated DPCs. An increased Bcl-2/Bax transcript ratio contributed to cellular proliferation, and this was maintained in the MPA-treated environment. Topically applied MPA promoted anagen hair follicle induction in mice. The effect of MPA on hair follicles was compatible with that of MXD, and this effect was accelerated by MN treatment. CONCLUSIONS: MPA promotes proliferation of DPCs and induction of anagen hair follicles in mice. This finding raises the possibility that MPA could be used as a treatment option for hair-loss disorders.

Autofluorescence analysis of dermatitis and squamous cell carcinoma in paraffin wax-embedded skin samples.

BACKGROUND: Recent research has investigated the use of autofluorescence (AF) for distinguishing between normal and cancerous tissues according to different fluorescence characteristics. AIM: To analyze if AF can help differentiate cancerous lesions from other nonneoplastic lesions, such as dermatitis, in each layer of the skin ex vivo. METHODS: Paraffin wax-embedded tissue samples were obtained from patients who were histopathologically diagnosed with squamous cell carcinoma (SCC), psoriasis, chronic dermatitis (lichen simplex chronicus, prurigo nodularis) or acute dermatitis (atopic dermatitis). AF intensity was measured in four layers of the epidermis (corneal, granular, spinous and basal) and two layers of the dermis (papillary and reticular). RESULTS: AF was highest in all layers of psoriasis samples compared with all layers of all other groups. Higher AF values were seen in SCC compared with all skin layers of acute and chronic dermatitis; this finding was especially true in the corneal layer, papillary dermis and reticular dermis. CONCLUSIONS: This ex vivo AF study provides basic data for future in vivo studies of AF as a noninvasive diagnostic tool.

Relationship between the HLA-G 14 bp insertion/deletion polymorphism and susceptibility to autoimmune disease: a meta-analysis.

Numerous studies have investigated the potential relationship between the human leukocyte antigen (HLA)-G 14-bp insertion/deletion (INS/DEL) polymorphisms and autoimmune disease (AID). However, published results are inconclusive. Our aim was to determine whether the 14-bp INS/DEL polymorphism in the HLA-G gene contributes to the risk of AID. A systemic literature search of the PubMed and EMBASE databases was conducted to identify eligible studies investigating the association of the HLA-G 14-bp INS/DEL polymorphism with AID. Our analysis included 11 publications involving a total of 6462 individuals. Overall, no significant association between the HLA-G 14-bp INS/DEL polymorphism and AID was detected in any comparison model. Further subgroup analyses based on AID types and ethnicity also revealed no significant associations. Our results suggest that the HLA-G 14-bp INS/DEL polymorphism is unrelated to the development of AID. Further studies including larger sample sizes are warranted to confirm these results.

Nonablative fractional laser as a tool to facilitate skin penetration of 5-aminolaevulinic acid with minimal skin disruption: a preliminary study.

BACKGROUND: Effective penetration of a photosensitizer is an essential step in photodynamic therapy (PDT). There have been trials of several methods, including laser treatment, to facilitate prompt and sufficiently deep transdermal drug delivery. OBJECTIVE: To evaluate the effects of nonablative fractional laser pretreatment on 5-aminolaevulinic acid (ALA) penetration of the skin. METHODS: Twelve treatment areas (1 × 1 cm(2)) on the backs of 10 healthy male subjects were mapped. Test areas received laser treatment followed by incubation with ALA. Laser treatment was performed with a 1550 nm fractional erbium glass laser, and the laser energy was set to 20 or 50 mJ with a spot density of 50 cm(-2). ALA incubation time was 30, 60 or 180 min. Porphyrin fluorescence was measured. RESULTS: Sites pretreated with nonablative fractional laser showed significantly increased porphyrin fluorescence compared with nonpretreated areas. Laser energy strength and ALA incubation time were positively correlated with ALA absorption. CONCLUSIONS: Nonablative fractional laser treatment effectively enhanced ALA skin penetration. Pretreatment with a nonablative fractional laser can be used for ALA-PDT to achieve higher ALA uptake and shortened ALA incubation times with minimal skin barrier disruption compared with ablative laser.

TLR9 gene polymorphism (rs187084, rs352140): association with acute rejection and estimated glomerular filtration rate in renal transplant recipients.

The Toll-like receptors (TLRs) are related to innate immunity. TLR9, a member of TLRs, is expressed in immune cell-rich tissues and mediates cellular response. We investigated the association between TLR9 polymorphisms and kidney allograft outcomes. To investigate whether TLR9 polymorphisms are associated with acute rejection after renal transplantation, two single nucleotide polymorphisms (SNPs) of TLR9 gene (rs187084 -1486; rs352140, G2848A) were selected and genotyped by direct sequencing in 342 renal transplant recipients. SNPStats, SNPAnalyzer, Helixtree and Haploview version 4.2 were used to analyse genetic data. Multiple logistic regression models (codominant, dominant, recessive and log-additive) were used to evaluate odds ratios (ORs), 95% confidence intervals (CIs) and P values. Both SNPs, TLR9 rs187084 -1486 and rs352140 G2848A, of recipients were associated with the risk of acute rejection in renal transplantation. C allele of rs187084 -1486 and A allele of rs352140 G2848A were protective genotype for acute rejection (OR 0.6, 95% CI 0.40-0.92; P = 0.018, OR 0.64, 95% CI 0.42-0.98; P = 0.04, respectively). rs187084 -1486 CT and rs352140 G2848A GA genotype were associated with a lower eGFR after a year of renal transplantation. TLR9 polymorphisms, rs187084 and rs352140, of recipients were associated with the risk of acute rejection in renal transplantation. The patients with rs187084 -1486 CT and rs352140 G2848A GA genotype showed a lower eGFR after a year of renal transplantation.

Purple urine bag syndrome: case report and literature review.

Purple urine bag syndrome (PUBS) is a medical syndrome in which there is purple discoloration of the urine of catheterized patients as well as discoloration of the collecting bag and the associated tubing. This rare condition, which mostly affects women, is generally associated with catheter-associated urinary tract infection, chronic constipation and alkaline urine. PUBS may be caused by sequential chemical reactions involving tryptophan from food in the gastrointestinal tract. The clinical course of PUBS is generally benign, and intensive treatment is not usually needed. We present 3 cases of this unusual and interesting phenomenon and a literature review.

Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population.

BACKGROUND: Vitiligo is a pigmentary skin disorder characterized by a chronic and progressive loss of melanocytes. Although the aetiology of vitiligo is currently unknown, several theories have been proposed to explain the pathogenesis of this disease, including autoimmune, neural, self-destruction, oxidative stress, and genetic theories. Thioredoxin domain containing 5 (TXNDC5) is a newly identified member of the thioredoxin family. TXNDC5 has a protein disulphide isomerase-like domain which plays an important role in protein folding and chaperone activity, against endoplasmic reticulum (ER) stress induced by oxidative stress within the ER. OBJECTIVES: To determine whether variation in the TXNDC5 gene contributes to the risk of developing nonsegmental vitiligo (NSV) in the Korean population. METHODS: We conducted a case-control association study of 230 patients with NSV and 417 matched, unaffected controls. Seven single nucleotide polymorphisms (SNPs) in the TXNDC5 gene were selected for study. RESULTS: Of the selected SNPs, three exonic SNPs (rs1043784, rs7764128 and rs8643) were statistically associated with NSV. Among them, rs1043784 remained a statistically significant association following Bonferroni correction. These three SNPs were located within a block of linkage disequilibrium; the haplotypes AGG and GAA, consisting of rs1043784, rs7764128 and rs8643, demonstrated a significant association with NSV. CONCLUSIONS: These results suggest that TXNDC5 gene polymorphisms are associated with the development of NSV in the Korean population.

Prognostic relevance of clinical and histological features in IgA nephropathy treated with steroid and angiotensin receptor blockers.

BACKGROUND: The prognostic relevance of clinical and histological features on renal outcome has not been assessed in patients with IgA nephropathy (IgAN) treated with the combination therapy of steroid and angiotensin receptor blockers (ARB). METHODS: A prospective trial of a combination of steroid and ARB was performed in 50 patients with IgAN, proteinuria and serum creatinine levels < 2 mg/dl. RESULTS: Over a mean follow-up period of 4 years, the combination therapy reduced proteinuria and hematuria and improved renal function in most patients. The mean change in estimated GFR (eGFR) was + 0.30 +/- 0.74 ml/min/1.73 m2/month. Forty-three patients (86%) exhibited stable renal function and 7 patients (14%) reached the primary end point of a (3) 20% decrease in eGFR from baseline levels. Between the nonprogressive and progressive patients, there were significant differences in the levels of urine protein/ creatinine excretion ratio (PCR) at baseline and throughout the follow-up period as well as baseline eGFR and degree of glomerular crescents (p < 0.05). Forty (80%) and 24 patients (48%) had a urine PCR < 1 and < 0.3 g/g, respectively, at their last follow-up. Renal survival was better in patients who had initial urine PCR < 3 g/g as well as final PCR < 1 g/g. Regression analysis revealed that the final urine PCR and age were critical determinants of slope of the eGFR by both univariate and multivariate analyses. However, eGFR, pathologic findings, systolic BP, proteinuria, and body mass index at the initial presentation were not predictive of slope. CONCLUSION: Our results indicate that achieving a low urinary protein excretion is the main determinant for the good outcome in patients treated with combination therapy.

Two cases of factitial panniculitis induced by electroacupuncture.

Factitial panniculitis can be produced by mechanical, physical, or chemical means. It often causes an unusual clinical and histological feature that defies diagnosis until self-inoculation or mechanical trauma is suspected and proved. Acupuncture has been used in East Asia for centuries as a method of treatment for various conditions, especially for pain relief, and is known to be a relatively safe system. The needles are often manipulated by hand once they are placed at the acupuncture points. Electroacupuncture, the application of pulsating electrical current to acupuncture needles, was developed in China as an extension of hand manipulation, and produces continuous and stronger stimulation; however, although this may provide more effective treatment, it may also provoke more mechanical trauma. We report two cases of factitial panniculitis in two young women, who presented with multiple subcutaneous nodules along the electroacupuncture sites.

Association of MCP-1 and CCR2 polymorphisms with the risk of late acute rejection after renal transplantation in Korean patients.

Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125-6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.

Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.

Everolimus-Induced Systemic Serositis After Simultaneous Liver and Kidney Transplantation: A Case Report.

Although everolimus, a mammalian target of rapamycin inhibitor, has been used as a potent immunosuppressive agent in organ transplantation, data regarding its adverse effect profile compared with that of sirolimus in clinical circumstances are limited. A 50-year-old man who underwent simultaneous liver and kidney transplantation 14 months previously was admitted with large pleural effusion, pericardial effusion, and ascites. Laboratory findings and cultures for possible infectious causes were all negative. Pericardial window surgery with drainage of the pericardial fluid was performed on day 3. Pleural and pericardial biopsy revealed non-specific inflammation without evidence of malignant cells. Everolimus was discontinued and replaced by mycophenolate mofetil on day 4. Significant clinical improvement was observed after discontinuation of everolimus, and follow-up echocardiography and chest radiography showed no recurrence of the pericardial or pleural effusion after discharge.

Association Studies of Bone Morphogenetic Protein 2 Gene Polymorphisms With Acute Rejection in Kidney Transplantation Recipients.

OBJECTIVE: Bone morphogenetic proteins (BMP) belong to the transforming growth factor beta superfamily of proteins. This study was performed to evaluate the association of BMP gene polymorphisms with acute renal allograft rejection (AR) and graft dysfunction (GD) in Koreans. METHODS: Three hundred thirty-one patients who had kidney transplantation procedures were recruited. Transplantation outcomes were determined in terms of AR and GD criteria. We selected six single nucleotide polymorphisms (SNPs): rs1979855 (5' near gene), rs1049007 (Ser87Ser), rs235767 (intron), rs1005464 (intron), rs235768 (Arg190Ser), and rs3178250 (3; untranslated region). RESULTS: Among the six SNPs tested, the rs235767, rs1005464, and rs3178250 SNPs were significantly associated with AR (P < .05). The rs1049007 and rs235768 SNPs also showed an association with GD (P < .05). CONCLUSIONS: In conclusion, these results suggest that the BMP2 gene polymorphism may be related to the development of AR and GD in kidney transplant recipients.

A Promoter Polymorphism in the CD46 Complement Regulatory Protein Gene Is Associated With Acute Renal Allograft Rejection.

OBJECTIVES: CD46 molecule (complement regulatory protein [CD46]), known as a human cell surface receptor, plays an important role in complement and T-cell regulation for organ transplantation. This study was performed to evaluate the association of promoter polymorphism (rs2796267, -496 A/G) of the CD46 gene with acute renal allograft rejection (AR), late acute rejection (LAR), and graft loss (GL) in Korean patients. METHODS: A total of 334 patients with kidney transplants were recruited. Transplantation outcomes were determined in terms of AR, LAR, and GL criteria. The promoter single nucleotide polymorphism (SNP) of CD46 was genotyped by direct sequencing. RESULTS: The rs2796267 SNP exhibited significant differences between the AR group and non-AR group (codominant1 model, P = .012; odds ratio [OR], 0.47 [95% confidence interval, 0.26-0.84]; dominant model, P = .012; OR, 0.50 [95% CI, 0.29-0.86]; and allele distribution, P = .034; OR, 0.64 [95% CI, 0.43-0.94]). In addition, the SNP also exhibited significant associations with LAR (codominant2 model, P = .041; OR, 0.12 [95% CI, 0.02-0.92]; recessive model, P = .005; OR, 0.13 [95% CI, 0.02-0.94]; and allele distribution, P = .038; OR, 0.58 [95% CI, 0.35-0.97]). CONCLUSIONS: This study suggests that the promoter polymorphism (rs2796267, -496 A/G) CD46 gene may be related to susceptibility of AR in Korean kidney transplantation recipients.