Performance of neuroretinal rim thickness measurement by Cirrus high-definition optical coherence tomography in myopic eyes.

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.

Comparative study of the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib versus methotrexate for disease-modifying antirheumatic drug-naïve patients with rheumatoid arthritis.

An assessment of the relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) was performed in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) so as to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and MTX in DMARD-naïve RA patients. Four RCTs comprising 2185 patients met the inclusion criteria. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of achieving the American College of Rheumatology 20% (ACR20) response rate, followed by baricitinib 4 mg, tofacitinib 5 mg, filgotinib 200 mg, and MTX. Tofacitinib, baricitinib, upadacitinib, and filgotinib treatments achieved significantly higher ACR50 and ACR70 responses compared to MTX. Tofacitinib 5 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. The safety analysis based on serious adverse events, adverse events (AEs), and withdrawals due to AEs revealed no statistically significant differences between the respective intervention groups. In conclusion, tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for DMARD-naïve RA patients, suggesting a difference in efficacy and safety among the different JAK inhibitors.

Recent advances in the development of gene delivery systems.

BACKGROUND: Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy. MAIN BODY: The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s. CONCLUSION: The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.

Simultaneously Targeting Myofibroblast Contractility and Extracellular Matrix Cross-Linking as a Therapeutic Concept in Airway Fibrosis.

Fibrosis after solid organ transplantation is considered an irreversible process and remains the major cause of graft dysfunction and death with limited therapies. This remodeling is characterized by aberrant accumulation of contractile myofibroblasts that deposit excessive extracellular matrix (ECM) and increase tissue stiffness. Studies demonstrate, however, that a stiff ECM itself promotes fibroblast-to-myofibroblast differentiation, stimulating further ECM production. This creates a positive feedback loop that perpetuates fibrosis. We hypothesized that simultaneously targeting myofibroblast contractility with relaxin and ECM stiffness with lysyl oxidase inhibitors could break the feedback loop, reversing established fibrosis. To test this, we used the orthotopic tracheal transplantation (OTT) mouse model, which develops robust fibrotic airway remodeling. Mice with established fibrosis were treated with saline, mono-, or combination therapies. Although monotherapies had no effect, combining these agents decreased collagen deposition and promoted re-epithelialization of remodeled airways. Relaxin inhibited myofibroblast differentiation and contraction in a matrix-stiffness-dependent manner through prostaglandin E2 (PGE2 ). Furthermore, the effect of combination therapy was lost in PGE2 receptor knockout and PGE2 -inhibited OTT mice. This study revealed the important synergistic roles of cellular contractility and tissue stiffness in the maintenance of fibrotic tissue and suggests a new therapeutic principle for fibrosis.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren's syndrome: a cohort study.

OBJECTIVES: Fatigue is a common clinical manifestation in patients with primary Sjögren's syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. METHOD: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. RESULTS: The median total ESSPRI score was 5 [interquartile range (IQR) 4-6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. CONCLUSIONS: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry.

Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.

A systematic review of diagnostic accuracy of vertebral fracture assessment (VFA) in postmenopausal women and elderly men.

UNLABELLED: This systematic review was performed to compare the diagnostic accuracy of vertebral fracture assessment (VFA) with that of spinal radiography for identification of vertebral fractures (VFs). VFA appeared to have moderate sensitivity and high specificity for detecting VFs when compared with spinal radiography. INTRODUCTION: VFs are recognized as the hallmark of osteoporosis, and a previous VF increases the risk of a future fracture. Therefore, the timely detection of VFs is important for prevention of further fractures. This systematic review examined the diagnostic accuracy of VFA using dual X-ray absorptiometry (DXA) to identify VFs. METHODS: We searched for potentially relevant studies using electronic databases, including Ovid-Medline, Ovid-EMBASE, Cochrane library, and four Korean databases, from their inception to May 2013. We compared the diagnostic accuracy of VFA with that of spinal radiography for detection of VFs by analyzing the sensitivity and specificity using a 2 × 2 contingency table. Subgroup analyses were also performed on studies with a low risk of bias and applicability. RESULTS: Twelve studies were analyzed for the diagnostic accuracy of VFA. The sensitivity and specificity were 0.70-0.93 and 0.95-1.00, respectively, analyzed on a per-vertebra basis, and 0.65-1.00 and 0.74-1.00 on a per-patient basis. The sensitivity and specificity of five studies in subgroups with a low risk of bias in the intervention test were 0.70-0.84 and 0.96-0.99, respectively. In studies with a low risk of bias in the patient selection, those based on a per-vertebra basis in three studies were 0.70-0.93 and 0.96-1.00, respectively. CONCLUSIONS: VFA had moderate sensitivity and high specificity for detecting VF when compared with spinal radiography. However, the present findings are insufficient to assess whether spinal radiography should be replaced by VFA.

Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection.

The loss of a functional microvascular bed in rejecting solid organ transplants is correlated with fibrotic remodeling and chronic rejection; in lung allografts, this pathology is predicted by bronchoalveolar fluid neutrophilia which suggests a role for polymorphonuclear cells in microcirculatory injury. In a mouse orthotopic tracheal transplant model, cyclosporine, which primarily inhibits T cells, failed as a monotherapy for preventing microvessel rejection and graft ischemia. To target neutrophil action that may be contributing to vascular injury, we examined the effect of a neutrophil elastase inhibitor, elafin, on the microvascular health of transplant tissue. We showed that elafin monotherapy prolonged microvascular perfusion and enhanced tissue oxygenation while diminishing the infiltration of neutrophils and macrophages and decreasing tissue deposition of complement C3 and the membrane attack complex, C5b-9. Elafin was also found to promote angiogenesis through activation of the extracellular signal-regulated kinase (ERK) signaling pathway but was insufficient as a single agent to completely prevent tissue ischemia during acute rejection episodes. However, when combined with cyclosporine, elafin effectively preserved airway microvascular perfusion and oxygenation. The therapeutic strategy of targeting neutrophil elastase activity alongside standard immunosuppression during acute rejection episodes may be an effective approach for preventing the development of irreversible fibrotic remodeling.

Ecklonia cava promotes hair growth.

BACKGROUND: Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses. AIM: We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and on hair growth in mice. METHODS: The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA. RESULTS: The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs. CONCLUSIONS: These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells.

Precuneus hypoperfusion plays an important role in memory impairment of patients with systemic lupus erythematosus.

The present study was designed to identify regional cerebral blood flow (rCBF) abnormalities in systemic lupus erythematosus (SLE) patients with memory impairments. Nineteen SLE patients (mean age 36.1 ± 8.6 years, range 17-47) with subjective memory complaints underwent brain single-photon emission computed tomography (SPECT). The Korean Wechsler Adult Intelligence Scale (K-WAIS) and the Rey-Kim Memory Test (RKMT) were used objectively to evaluate cognitive functions in these patients. On the basis of the Intelligence Quotient-Memory Quotient (IQ-MQ) difference score, patients were classified into two groups: those with below one standard deviation (SD) from the mean for normal subjects of comparable age and education (memory impairment, n = 6) and those with without memory impairment (non-memory impairment, n = 13). Their brain SPECT images were analyzed by statistical parametric mapping (SPM) for group comparisons. The group of SLE patients with memory impairment showed significant hypoperfusion in the right precuneus compared with those with non-memory impairment (p < 0.001). Hypoperfusion of the precuneus may play a significant role in the memory function of SLE patients. SPM analysis of brain SPECT images could be a useful and objective tool for identifying abnormal rCBF in SLE patients with memory impairment.

l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase.

BACKGROUND: l-Ascorbic acid 2-phosphate (Asc 2-P), a derivative of l-ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice. OBJECTIVES: To investigate whether the promotion of hair growth by Asc 2-P is mediated by insulin-like growth factor-1 (IGF-1) and, if so, to investigate the mechanism of the Asc 2-P-induced IGF-1 expression. METHODS: Dermal papilla (DP) cells were cultured and IGF-1 level was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay after Asc 2-P treatment in the absence or presence of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2-P treatment in the absence or presence of neutralizing antibody against IGF-1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2-P treatment in the absence or presence of LY294002 was examined by Ki-67 immunostaining. RESULTS: IGF-1 mRNA in DP cells was upregulated and IGF-1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2-P. Immunohistochemical staining showed that IGF-1 staining is increased in the DP of cultured human hair follicles by Asc 2-P. The neutralizing antibody against IGF-1 significantly suppressed the Asc 2-P-mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2-P-induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2-P-inducible IGF-1 expression and proliferation of follicular keratinocytes in cultured hair follicles. CONCLUSIONS: These data show that Asc 2-P-inducible IGF-1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

There have been many genetic studies of systemic lupus erythematosus (SLE) in Asia, but the status of SLE in Asia remains unclear. Genes that have been associated with SLE in Caucasians have shown both consistent and inconsistent results in Asians. This prompted us to review studies of SLE-associated genes and compare the degree of consistency according to ethnicity in Asia. We searched PubMed and the national databases in Korea and Japan for SLE genetic studies. A total of 755 articles were found and after applying various exclusion criteria, 442 studies including 17 linkage studies, 2 genome-wide association studies and 423 candidate-gene analyses were reviewed. Nine linkage loci were confirmed to be associated with SLE susceptibility in non-Asians, but the risk locus (16q12) has been identified in only one Asian study. A total of 156 candidate genes were analyzed, of which 92 were studied in Asians. Although there were allelic (HLA-DRB1 and IRF5) or genetic heterogeneity (FCGR gene family), HLA-DRB1, the FCGR gene family, IRF5, STAT4 and MECP2 showed consistent associations with SLE susceptibility across ethnicities. In conclusion, genetic associations often vary with ethnicity, requiring validation in different ethnic groups, and hence future SLE genetic studies will require strong worldwide collaborations.

A regulatory SNP at position -899 in CDKN1A is associated with systemic lupus erythematosus and lupus nephritis.

The CDKN1A gene encoding a cell cycle inhibitor, p21(WAF1/CIP1), is located in the systemic lupus erythematosus (SLE) susceptibility locus on chromosome 6p21.2. Decreased cellular levels of p21 are associated with SLE. Here, we examine four single-nucleotide polymorphisms (SNPs) within the promoter and two in the first intron of CDKN1A for association with SLE susceptibility. A comparison of 742 Korean SLE patients with 1017 controls disclosed that one SNP (rs762624 C>A at position -899), located at a putative Myb-binding site in the promoter, was associated with SLE susceptibility (P=0.00047). This association was independent of the SLE-association signal of HLA-DRB1 on 6p21.3, as it was significant after adjustment for SLE-risk DRB1 alleles (P=0.0012). The same SNP was associated with lupus nephritis (P=0.000014). The risk allele-carrying promoter sequence displayed approximately 15% lower activity than the non-risk sequence upon fusion to the luciferase gene (P=0.025). Endogenous CDKN1A mRNA levels measured in Epstein-Barr virus-transformed B cells established from 16 control subjects were linearly correlated with a decreasing copy number of the risk allele (P=0.024). Accordingly, we conclude that the minor allele A at -899 of CDKN1A is associated with increased susceptibility to SLE and lupus nephritis, and decreased cellular levels of p21.

MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients.

OBJECTIVE: The MER receptor tyrosine kinase (MERTK) gene is critical for the efficient clearance of apoptotic cells and has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the genetic polymorphisms in MERTK to evaluate it as a potential candidate gene for a host genetic study of SLE and clinical manifestations in patients with SLE. METHODS: By resequencing the coding and flanking regions of the MERTK gene in 24 unrelated Koreans, 37 polymorphisms were identified. Based on gene position, minor allele frequency and inter-single-nucleotide polymorphism (SNP) linkage disequilibrium, six of these polymorphisms were selected for subsequent genotyping and association analysis with the risk of SLE and haematological disorders in 350 Korean SLE patients and 330 controls. RESULTS: Although no significant associations with the risk of SLE were found, logistic regression analyses revealed that variants +465C > G (P = 0.05) and +130215insdelT (P = 0.0005) were significantly associated with decreased risk of leucopenia in SLE patients. Further, +465C > G, +95616G > A, +123157A > G and the haplotype ht1 also showed significant associations (P = 0.006-0.05) with a decreased risk of lymphopenia in SLE patients. CONCLUSION: Our findings suggest that polymorphisms in MERTK might be one of the genetic risk factors for presenting leucopenia and lymphopenia in SLE patients.

Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to confirm whether polymorphisms of the poly(ADP-ribose) polymerase gene (PARP) are associated with genetic susceptibility to systemic lupus erythematosus (SLE) and to investigate the possible association of nephritis and arthritis in SLE with PARP polymorphisms. METHODS: Using direct DNA sequencing in 24 individuals, we identified 44 sequence variants within exons and their flanking regions, including the 1.5-kb promoter region of PARP. Six common polymorphic sites were selected for larger-scale genotyping (in 350 Korean SLE patients and 330 healthy controls), which identified six common haplotypes. RESULTS: Although no statistically significant association with the risk of SLE was observed, we found that two single-nucleotide polymorphisms (SNPs -1963A --> G and +28077G --> A) were significantly associated with an increased risk of nephritis, and one non-synonymous variant [+40329T --> C(V762A)] was also significantly associated with an increased risk of arthritis, while the -1963A --> G SNP showed a protective effect on arthritis in Korean SLE patients. CONCLUSION: Our results demonstrate that PARP polymorphisms are not associated with SLE susceptibility, but that -1963A --> G, +28077G --> A and +40329T --> C(V762A) are significantly associated with nephritis and arthritis in Korean SLE patients.

Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index in systemic lupus erythematosus.

OBJECTIVE: Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). We examined the IL10 genotype of Korean patients with SLE and normal controls to determine whether associations exist between the pattern of inherited IL10 genes and SLE susceptibility or the SLICC/ACR Damage Index (SDI). METHODS: A total of 350 Korean SLE patients and 330 healthy subjects were enrolled. Direct DNA sequencing and primer extension procedures were employed. Logistic regression analyses were performed to examine the genetic association with SLE and SDI. RESULTS: Eight sequence variants were identified by direct DNA sequencing in 24 Korean individuals. Five of the polymorphisms were selected for larger scale genotyping (n = 680) by considering their allele frequencies, haplotype-tagging status and linkage disequilibrium coefficients among polymorphisms. Haplotypes and allele distributions of the IL10 polymorphisms did not differ significantly between SLE patients and controls. Among identified SNPs, the rare C allele of IL10-592A-->C was significantly associated with the SDI among SLE patients in the following three alternative models: codominant (P = 0.007, odds ratio = 1.70), dominant (P = 0.02, odds ratio = 1.85) and recessive (P = 0.05, odds ratio = 2.25). Similarly, IL10+955T-->G and IL10-ht2 were significantly associated with the SDI in the codominant and dominant models. CONCLUSION: IL10 polymorphisms are not associated with disease susceptibility in Korean patients with SLE. However, IL10-592A-->C, IL10+955T-->G and IL10-ht2 are significantly associated with the SDI, suggesting that IL10-592C, IL10+955G and IL10-ht2 accelerate the damage induced by SLE.

Catalase and PPARgamma2 genotype and risk of systemic lupus erythematosus in Koreans.

Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2) are important regulators of oxidative stress and inflammation, which may contribute to the development of systemic lupus erythematosus (SLE). The objective of this study was to investigate the effects of genetic polymorphisms of CAT and PPARy2 on risk and severity of SLE in a Korean population. DNA was isolated from blood samples collected from 345 patients with SLE and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the Pro 12Ala polymorphism of PPARgamma2 were performed by PCR-RFLP analysis. The severity of SLE was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). No association was observed between genotypes for any of the clinical manifestations of SLE. CAT and PPARgamma2 genotypes were not associated with either risk or severity of SLE. For subjects who were carriers of the high activity T allele for CAT and have the Pro/Pro genotype for PPARgamma2, the odds ratio (95% confidence interval) for risk of SLE was 0.45 (0.23-1.08). Our results suggest that genetic polymorphisms of CAT and PPARy2 do not play a significant role in the development of SLE in a Korean population. A possible protective effect of a combined genotype warrants further investigation.

Development of biomaterials for gene therapy.

Novel biocompatible polymeric gene carriers have been examined for their potential in treating various genetic and acquired diseases. The use of polymeric gene carriers may overcome the current problems associated with viral vectors in safety, immunogenicity, and mutagenesis. However, effective polymer-based gene therapy requires the control of cellular access and uptake, intracellular trafficking, and nuclear retention of plasmid DNA. Inefficient endosomal release, cytoplasmic transport, and nuclear entry of plasmids are currently limiting factors in the use of polymers for effective plasmid-based gene therapy. Therefore, several different polymeric gene carriers have been designed recently in an attempt to overcome these problems. This review explores the conceptual and experimental aspects of polymer-based gene delivery and presents an overview on the recent use of polymers to enhance the effectiveness of plasmid-based systems. Despite their current limitations, polymeric carriers have significant potential as commercially viable gene medicines.