The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

Development of Agrobacterium-mediated in planta transformation protocol through coleoptile in rice.

Genetic modification of rice is mainly carried out by Agrobacterium-mediated transformation of callus accompanied by tissue culture. It is time consuming, laborious and unapplicable for cultivars unable to induce callus. In this study, we have reported a novel gene transfer protocol that involves pulling out primary leaf from coleoptile and injection of Agrobacterium culture into the empty channel. Out of 25 plants survived after injection of Agrobacterium tumefaciens EHA105 culture harboring pCAMBIA1301-RD29A-AtDREB1A, 8 T0 plants revealed the expected size of around 811 bp corresponding to AtDREB1A gene and Southern blotting analysis on 18 T1 plants suggested introgression of AtDREB1A. 3 T2 lines (7-9, 12-3, 18-6) exhibited accumulation of free proline and soluble sugars, yet increase of chlorophyll content, but decrease of electrolyte leakage and methane dicarboxylic aldehyde under cold stress condition at the vegetative growth stage. Yield components investigation on T2 lines showed earlier heading date and no yield loss compared to wild type plants grown under normal condition. GUS expression analysis and integrated transgene detection in T0 and T1 plants followed by evaluation of cold stress tolerance in T2 lines suggest the advantage of this in planta transformation protocol to obtain transgenic rice.

Increased risk of suicidality in patients with psoriasis: A Nationwide cohort study in Korea.

BACKGROUND: Psoriasis has a devastating psychological impact on patients' quality of life. However, the relationship between suicidality and psoriasis remains unclear. OBJECTIVE: This study analysed and compared the risk of suicidality (suicidal ideation, suicide attempt and completed suicide) between patients with psoriasis and the general population. METHODS: This nationwide, population-based, retrospective, cohort study analysed the Korean National Health Insurance Service claim data from 2005 to 2018. RESULTS: The study included 348,439 patients with psoriasis aged over 18 years and with age- and sex-matched controls. The risk of suicidality was higher in the psoriasis group than in the control group [adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI), 1.18-1.24]. The aHR of suicidality was higher in the psoriatic arthritis group (aHR, 1.46; 95% CI, 1.39-1.54) than in the psoriasis-alone group (aHR, 1.17; 95% CI, 1.13-1.20). However, the severity of psoriasis and suicidality showed no correlation (mild psoriasis group: aHR, 1.22; 95% CI, 1.18-1.25; moderate-to-severe psoriasis group: aHR, 1.16; 95% CI, 1.10-1.23). CONCLUSION: Patients with psoriasis have an increased risk of suicidality. In particular, the presence of arthritis in patients had a more significant effect on the risk of suicidality.

Insensitive Effects of Inflammatory Cytokines on the Reference Genes of Synovial Fluid Resident-Mesenchymal Stem Cells Derived from Rheumatoid Arthritis Patients.

Mesenchymal stem cells derived from rheumatoid arthritis patients (RA-MSCs) provide an understanding of a variety of cellular and immunological responses within the inflammatory milieu. Sustained exposure of MSCs to inflammatory cytokines is likely to exert an influence on genetic variations, including reference genes (RGs). The sensitive effect of cytokines on the reference genes of RA-SF-MSCs may be a variation factor affecting patient-derived MSCs as well as the accuracy and reliability of data. Here, we comparatively evaluated the stability levels of nine RG candidates, namely GAPDH, ACTB, B2M, EEF1A1, TBP, RPLP0, PPIA, YWHAZ, and HPRT1, to find the most stable ones. Alteration of the RG expression was evaluated in MSCs derived from the SF of healthy donors (H-SF-MSCs) and in RA-SF-MSCs using the geNorm and NormFinder software programs. The results showed that TBP, PPIA, and YWHAZ were the most stable RGs for the normalization of H-SF-MSCs and RA-SF-MSCs using RT-qPCR, whereas ACTB, the most commonly used RG, was less stable and performed poorly. Additionally, the sensitivity of RG expression upon exposure to proinflammatory cytokines (TNF-α and IL-1ß) was evaluated. RG stability was sensitive in the H-SF-MSCs exposed to TNF-α and IL-1ß but insensitive in the RA-SF-MSCs. Furthermore, the normalization of IDO expression using ACTB falsely diminished the magnitude of biological significance, which was further confirmed with a functional analysis and an IDO activity assay. In conclusion, the results suggest that TBP, PPIA, and YWHAZ can be used in SF-MSCs, regardless of their exposure to inflammatory cytokines.

Highly Sensitive and Selective Detection of Hydrogen Using Pd-Coated SnO2 Nanorod Arrays for Breath-Analyzer Applications.

We report a breath hydrogen analyzer based on Pd-coated SnO2 nanorods (Pd-SnO2 NRs) sensor integrated into a miniaturized gas chromatography (GC) column. The device can measure a wide range of hydrogen (1-100 ppm), within 100 s, using a small volume of human breath (1 mL) without pre-concentration. Especially, the mini-GC integrated with Pd-SnO2 NRs can detect 1 ppm of H2, as a lower detection limit, at a low operating temperature of 152 °C. Furthermore, when the breath hydrogen analyzer was exposed to a mixture of interfering gases, such as carbon dioxide, nitrogen, methane, and acetone, it was found to be capable of selectively detecting only H2. We found that the Pd-SnO2 NRs were superior to other semiconducting metal oxides that lack selectivity in H2 detection. Our study reveals that the Pd-SnO2 NRs integrated into the mini-GC device can be utilized in breath hydrogen analyzers to rapidly and accurately detect hydrogen due to its high selectivity and sensitivity.

Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators.

Abnormalities in animals cloned via somatic cell nuclear transfer (SCNT) have been reported. In this study, to produce bomb-sniffing dogs, we successfully cloned four healthy dogs through SCNT using the same donor genome from the skin of a male German shepherd old dog. Veterinary diagnosis (X-ray/3D-CT imaging) revealed that two cloned dogs showed normal phenotypes, whereas the others showed abnormal shortening of the mandible (brachygnathia inferior) at 1 month after birth, even though they were cloned under the same conditions except for the oocyte source. Therefore, we aimed to determine the genetic cause of brachygnathia inferior in these cloned dogs. To determine the genetic defects related to brachygnathia inferior, we performed karyotyping and whole-genome sequencing (WGS) for identifying small genetic alterations in the genome, such as single-nucleotide variations or frameshifts. There were no chromosomal numerical abnormalities in all cloned dogs. However, WGS analysis revealed variants of Wnt signaling pathway initiators (WNT5B, DVL2, DACT1, ARRB2, FZD 4/8) and cadherin (CDH11, CDH1like) in cloned dogs with brachygnathia inferior. In conclusion, this study proposes that brachygnathia inferior in cloned dogs may be associated with variants in initiators and/or regulators of the Wnt/cadherin signaling pathway.

Differences in foot skin microbiomes between patients with type 2 diabetes and healthy individuals.

Impaired immunity and changes in the microenvironment in patients with diabetes might influence the composition of the cutaneous microbiome. However, data on the cutaneous microbiome of these patients are scarce. This study compared the fungal and bacterial components of the skin microbiome between patients with type 2 diabetes mellitus (DM) and healthy individuals. We obtained skin swab samples from the plantar forefoot of 17 patients with DM and 18 healthy individuals to conduct a cross-sectional study. The samples were profiled with culture-independent sequencing of the V3 to V4 regions of the bacterial 16S rRNA gene and the fungal ITS2 region, followed by direct DNA extraction and molecular polymerase chain reaction (PCR). We observed a differential cutaneous microbiome, especially for fungi, in patients with type 2 diabetes compared to that in healthy controls. Trichophyton rubrum was more abundant in DM samples. The Shannon diversity index for fungi was lower in the DM patients. Principal coordinate analysis plots and permutational multivariate analysis of variance (PERMANOVA) tests based on Bray-Curtis distances between samples supported the association of the fungal microbiome with DM at the species level. The results suggest that clinicians should pay attention to both fungi and bacteria and provide appropriate prevention and therapeutic strategies for diabetic cutaneous complications including diabetic foot ulcers. These data also contribute to future research associated with diabetes and cutaneous microbiomes.

Breath Acetone Measurement-Based Prediction of Exercise-Induced Energy and Substrate Expenditure.

The purpose of our study was to validate a newly developed breath acetone (BrAce) analyzer, and to explore if BrAce could predict aerobic exercise-related substrate use. Six healthy men ran on a treadmill at 70% of maximal oxygen consumption (VO2max) for 1 h after two days of a low-carbohydrate diet. BrAce and blood ketone (acetoacetate (ACAC), beta-hydroxybutyrate (BOHB)) levels were measured at baseline and at different time points of post-exercise. BrAce values were validated against blood ketones and respiratory exchange ratio (RER). Our results showed that BrAce was moderately correlated with BOHB (r = 0.68, p < 0.01), ACAC (r = 0.37, p < 0.01) and blood ketone (r = 0.60, p < 0.01), suggesting that BrAce reflect blood ketone levels, which increase when fat is oxidized. Furthermore, BrAce also negatively correlated with RER (r = 0.67, p < 0.01). In our multiple regression analyses, we found that when BMI and VO2max were added to the prediction model in addition to BrAce, R2 values increased up to 0.972 at rest and 0.917 at 1 h after exercise. In conclusion, BrAce level measurements of our BrAce analyzer reflect blood ketone levels and the device could potentially predict fat oxidation.

Pancreatic endocrine-like cells differentiated from human umbilical cords Wharton's jelly mesenchymal stem cells using small molecules.

Following success of pancreatic islet transplantation in the treatment of Type I diabetes mellitus, there is a growing interest in using cell-based treatment approaches. However, severe shortage of donor islets-pancreas impeded the growth, and made researchers to search for an alternative treatment approaches. In this context, recently, stem cell-based therapy has gained more attention. The current study demonstrated that epigenetic modification improves the in vitro differentiation of Wharton's jelly mesenchymal stem cells (WJMSCs) into pancreatic endocrine-like cells. Here we used two histone deacetylase (HDAC) inhibitors namely trichostatin A (TSA) and TMP269. TSA inhibits both class I and II HDACs whereas TMP269 inhibits only class IIa HDACs. WJMSCs were differentiated using a multistep protocol in a serum-free condition with or without TSA pretreatment. A marginal improvement in differentiation was observed after TSA pretreatment though it was not significant. However, exposing endocrine precursor-like cells derived from WJMSCs to TMP269 alone has significantly improved the differentiation toward insulin-producing cells. Further, increase in the expression of paired box 4 (PAX4), insulin, somatostatin, glucose transporter 2 (GLUT2), MAF bZIP transcription factor A (MAFA), pancreatic duodenal homeobox 1 (PDX-1), and NKX6.1 was observed both at messenger RNA and protein levels. Nevertheless, TMP269-treated cells secreted higher insulin upon glucose challenge, and demonstrated increased dithizone staining. These findings suggest that TMP269 may improve the in vitro differentiation of WJMSCs into insulin-producing cells.

Baicalin improves the in vitro developmental capacity of pig embryos by inhibiting apoptosis, regulating mitochondrial activity and activating sonic hedgehog signaling.

Baicalin, a traditional Chinese medicinal monomer whose chemical structure is known, can be used to treat female infertility. However, the effect of baicalin on embryonic development is unknown. This study investigated the effects of baicalin on in vitro development of parthenogenetically activated (PA) and in vitro fertilized (IVF) pig embryos and the underlying mechanisms involved. Treatment with 0.1 µg/ml baicalin significantly improved (P < 0.05) the in vitro developmental capacity of PA pig embryos by reducing the reactive oxygen species (ROS) levels and apoptosis and increasing the mitochondrial membrane potential (ΔΨm) and ATP level. mRNA and protein expression of sonic hedgehog (SHH) and GLI1, which are related to the SHH signaling pathway, in PA pig embryos at the 2-cell stage, were significantly higher in the baicalin-treated group than in the control group. To confirm that the SHH signaling pathway is involved in the mechanism by which baicalin improves embryonic development, we treated embryos with baicalin in the absence or presence of cyclopamine (Cy), an inhibitor of this pathway. Cy abolished the effects of baicalin on in vitro embryonic development. In conclusion, baicalin improves the in vitro developmental capacity of PA and IVF pig embryos by inhibiting ROS production and apoptosis, regulating mitochondrial activity and activating SHH signaling.

First-Principles Study on Structural, Electronic, and Optical Properties of Inorganic Ge-Based Halide Perovskites.

Using density functional theory calculations, we explore the structural, electronic, and optical properties of the inorganic Ge-based halide perovskites AGeX3 (A = Cs, Rb; X = I, Br, Cl) that can possibly be used as light absorbers. We calculate the lattice parameters of the rhombohedral unit cell with an R3 m space group, frequency-dependent dielectric constants, photoabsorption coefficients, effective masses of charge carriers, exciton binding energies, and electronic band structures by use of PBEsol and HSE06 functionals with and without SOC effect. We also predict the absolute electronic energy levels with respect to the external vacuum level by using the (001) surfaces with AX and GeX2 terminations, demonstrating their strong dependence on the surface terminations. The calculated results are found to be in reasonable agreement with the available experimental data for the cases of CsGeX3, while for the cases of RbGeX3 they are predicted for the first time in this work. We reveal that replacement of Cs with Rb can offer reasonable flexibility in optoelectronic properties matching for solar cell design and optimization, while X anion exchange gives rise to large changes.

Risk factors for increased serum creatinine level in patients with psoriasis treated with cyclosporine in a real-world practice.

Nephrotoxicity is a major concern for patients with psoriasis using cyclosporine. Here, we evaluated the impact of intermittent cyclosporine treatment on nephrotoxicity risk among patients with psoriasis in real-world clinical practice. We retrospectively reviewed 611 patients with psoriasis treated with cyclosporine between January 2013 and January 2017, 398 of whom were considered eligible for analysis. Eighteen (4.5%) patients showed a greater than 25% increase in serum creatinine levels. Age over 60 years (relative risk [RR], 1.6; p = .015), diabetes (RR, 2.3; p < .001), and obesity (RR, 1.7; p = .011) were the significant risk factors of increased serum creatinine levels in patients with psoriasis. There was no significant association of the treatment duration or cumulative dose of cyclosporine with increased serum creatinine levels. In real clinical practice, intermittent cyclosporine use with regular serum creatinine tests can be used to treat psoriasis relatively safely. Age over 60 years, diabetes and obesity are significant risk factors for cyclosporine-induced nephrotoxicity.

Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema.

BACKGROUND: Botulinum toxin (BTX) has been used cosmetically with good clinical efficacy and tolerable safety. OBJECTIVE: This randomized, double-blind, split-face clinical study aimed to investigate the efficacy and safety of intradermal BTX in patients with rosacea. MATERIALS AND METHODS: Twenty-four participants were enrolled and randomly given intradermal injections of BTX and normal saline in both cheeks. Clinician Erythema Assessment (CEA) score, Global Aesthetic Improvement Scale (GAIS) score, skin hydration, transepidermal water loss (TEWL), melanin content, erythema index, elasticity, and sebum secretions were evaluated at baseline and 2, 4, 8, and 12 weeks. RESULTS: On the BTX-treated side, the CEA score significantly decreased and the GAIS score significantly increased. The erythema index decreased at Weeks 4 and 8. Skin elasticity was improved at Weeks 2 and 4 and skin hydration, at Weeks 2, 4, and 8. However, TEWL and sebum secretion did not show significant differences. CONCLUSION: Intradermal BTX injections reduced erythema and rejuvenated the skin effectively and safely in patients with rosacea.

Comparison of internal organs between myostatin mutant and wild-type piglets.

BACKGROUND: Myostatin (MSTN) negatively regulates skeletal muscle development; however, its functions in internal organs have not been thoroughly investigated. Here, we compared the morphological, molecular, and biological characteristics of the heart, liver, spleen, lungs, kidneys, and tongue of homozygous MSTN mutant (MSTN-/- ), heterozygous MSTN mutant (MSTN+/- ), and wild-type (WT) piglets. RESULTS: The heart and liver were lighter in MSTN-/- piglets than in MSTN+/- piglets, while the tongue was heavier in MSTN-/- piglets than in WT piglets (P < 0.05). Furthermore, the tongue was longer in MSTN-/- piglets than in WT piglets, and myofibers of the tongue were significantly larger in the former piglets than in the latter ones (P < 0.01). mRNA expression of MSTN in all organs was significantly lower in MSTN-/- and MSTN+/- piglets than in WT piglets (P < 0.05). Meanwhile, mRNA expression of follistatin, which is closely related to MSTN, in the heart and liver was significantly higher in MSTN-/- piglets than in MSTN+/- and WT piglets (P < 0.05). In addition, protein expression of MSTN in the heart, kidneys, and tongue was significantly lower in MSTN-/- piglets than in WT piglets (P < 0.01). CONCLUSION: These results suggest that MSTN is widely expressed and has marked effects in multiple internal organs. Myostatin has crucial functions in regulating internal organ size, especially the tongue. © 2019 Society of Chemical Industry.

Analysis of the skin mycobiome in adult patients with atopic dermatitis.

With the recent availability of culture-independent sequencing methods, studies have been conducted to analyse skin micro-organisms present in patients with atopic dermatitis (AD). However, the database on the skin fungal communities, "mycobiome," has been relatively restrictive compared with the bacterial world. We aimed to comparatively analyse the overall skin mycobiome between patients with AD and healthy individuals in the Korean population. We analysed skin swab samples obtained from the antecubital fossae of 8 patients with AD and 8 healthy controls. Using sequencing method followed by direct DNA extraction and molecular PCR, taxonomic compositions of fungi at stepwise level ranks were analysed. The phylogenic marker used was internal transcribed spacer 2 regions of DNA. We observed the tendency of higher intra- and interpersonal taxonomic diversity at genus and species levels in AD samples. Non-Malassezia fungal diversity was also noticeable in the patient group compared with healthy controls. Malassezia globosa and Malassezia restricta were prevalent in all samples across both study groups, and some Malassezia species, including Malassezia sloofiae and Malassezia dermatis, characterized AD. Our data might provide a new insight into the mycobiome of adult AD, which contributes to building a systemic mycobiome database in AD.

Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer.

Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity-associated-interacting protein 5 overexpression promoted cell survival, preventing docetaxel-induced mitochondrial clearance. Conversely, short interfering RNA-mediated knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 accelerated docetaxel-induced apoptosis while increasing mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum stress and decreasing adenosine triphosphate production. We also found that the mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin homolog-induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity-associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown altered Neisseria gonorrhoeae opacity-associated-interacting protein 5 expression. These findings indicate that Neisseria gonorrhoeae opacity-associated-interacting protein 5 modulates docetaxel-induced mitophagic cell death and therefore suggest that this protein comprises a potential therapeutic target for gastric cancer treatment.

Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study.

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

Treatment of periorbital wrinkles using multipolar fractional radiofrequency in Korean patients.

A limited number of studies have evaluated the efficacy and safety of electrode pin fractional radiofrequency (FRF) for periorbital wrinkle treatment in Asian patients, but none have measured noninvasive methodological objective parameters such as periorbital wrinkle area. This study aimed to investigate the efficacy and safety of electrode pin multipolar FRF for the improvement of periorbital wrinkles in Korean patients by using a noninvasive methodological objective parameter. Seventy female subjects with periorbital wrinkles (age range, 40-60 years) participated in this study. Each patient underwent three sessions of FRF treatment to the periorbital region separated by 2-week intervals. The area of periorbital wrinkles was analyzed by using a Robo Skin Analyzer CS50 at 4 weeks after the final treatment session. Periorbital wrinkle area was significantly decreased at 1-month follow-up (75.77 ± 29.46 mm2) compared to baseline (94.74 ± 31.62 mm2). The improvement ratio of periorbital wrinkle area was 20.02 %. Side effects were limited to transient mild erythema, swelling, and crusts. Pain was tolerable without local anesthesia. Our findings suggest that the multipolar electrode pin FRF can be an effective and safe method for reducing periorbital wrinkles in Asian patients.

Isolation and identification of Malassezia species from Chinese and Korean patients with seborrheic dermatitis and in vitro studies on their bioactivity on sebaceous lipids and IL-8 production.

We investigated the distribution of Malassezia yeast in 120 Chinese (20 patients from each of six cities) and 20 Korean patients with scalp seborrheic dermatitis (SD) and dandruff (SD/D) using ITS1 and ITS2 polymerase chain reaction-restriction fragment length polymorphism. Bioactivity was studied by quantifying sebum lipid production by human primary sebocytes and inflammatory cytokine, interleukin-8 (IL-8) production was studied by exposing HaCaT keratinocytes with extracts of five standard Malassezia strains; M. globosa, M. restricta, M. sympodialis, M. dermatis and M. slooffiae. M. restricta and M. globosa were the most frequently encountered species from both Chinese and Korean patients. These two Malassezia species also promoted neutral lipid synthesis although the result was not statistically significant and induced significant increase in IL-8 production among the five Malassezia species studied. The study suggests a possible role of these organisms in the pathogenesis of SD/D.

A multicenter, randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly, the combination of etanercept 25 mg twice weekly and acitretin, and acitretin alone in patients with moderate to severe psoriasis.

BACKGROUND: Etanercept, a soluble tumor necrosis factor receptor, and acitretin have been shown to be effective in treating psoriasis. Acitretin is widely used in Korea. However, the combination of etanercept plus acitretin has not been evaluated among Korean patients with psoriasis. The objective of this study was to investigate the efficacy and safety of combination therapy with etanercept and acitretin in patients with moderate to severe plaque psoriasis. METHODS: Sixty patients with psoriasis were randomized to receive etanercept 50 mg twice weekly (BIW) for 12 weeks followed by etanercept 25 mg BIW for 12 weeks (ETN-ETN); etanercept 25 mg BIW plus acitretin 10 mg twice daily (BID) for 24 weeks (ETN-ACT); or acitretin 10 mg BID for 24 weeks (ACT). The primary efficacy measurement was the proportion of patients achieving 75 % improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Secondary end points included 50 % improvement in PASI (PASI 50) at week 24 and clear/almost-clear by Physician Global Assessment (PGA) at each visit through week 24. RESULTS: The proportions of patients achieving PASI 75, PASI 50, and PGA clear/almost-clear at week 24 in the ETN-ETN (52.4, 71.4, and 52.4 %, respectively) and ETN-ACT groups (57.9, 84.2, and 52.6 %, respectively) were higher than in the ACT group (22.2, 44.4, and 16.7 %, respectively). The incidence of adverse events was similar across all arms. This was an open-label study with a small number of patients. CONCLUSION: In Korean patients with moderate to severe plaque psoriasis, etanercept alone or in combination with acitretin was more effective than acitretin. All treatments were well tolerated throughout the study. TRIAL REGISTRATION: This study was registered on July 7, 2009 at ClinicalTrials.gov, NCT00936065 .