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TNF, IL12B, and IFNG Gene Polymorphisms in Serbian Patients with Psoriasis
( Svetlana Popadic ),( Emina Savic ),( Milos Markovic ),( Zorica Ramic ),( Ljiljana Medenica ),( Vera Pravica ),( Zorica Spuran ),( Vladimir Trajkovic ),( Dusan Popadic ) 대한피부과학회 2015 Annals of Dermatology Vol.27 No.2
Background: Psoriasis is a common chronic inflammatory skin disease with a strong genetic basis. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) such are IL-12 and IL-23, and interferon gamma (IFN-γ) are released from various inflammatory and resident cells, and have been implicated in the initiation/maintenance of inflammation. Certain alleles of the aforementioned cytokines may be associated with disease susceptibility/severity. Objective: To investigate the association of three common functional gene polymorphisms, namely TNF -308 G/A (rs1800629), IL12B (encoding the p40 subunit of IL-12/23) +1188 A/C (rs3212227), and IFNG +874 T/A (rs2430561) with psoriasis development and severity in Serbian patients. Methods: We genotyped 130 patients with psoriasis (26 of whom also had psoriatic arthritis) and 259 controls; rs1800629 and rs3212227, and rs2430561, by real-time PCR assay. Results: The TNF GG genotype was detected at a higher frequency in patients with psoriasis compared to control subjects (OR, 1.420; 95% CI, 0.870∼2.403) without statistical significance (p= 0.191). Lack of the TNF G allele was associated with lower psoriasis severity (p=0.007). The IL12B AC genotype was underrepresented in the patients with psoriatic arthritis compared to healthy subjects (OR, 0.308; 95% CI, 0.090∼ 1.057; p=0.049). The distribution of the rs2430561 allele and genotype frequencies was similar between patients with psoriasis and controls. Conclusion: Our study demonstrates an effect of the rs1800629 on psoriasis severity, and a marginal impact of the rs3212227 on susceptibility to psoriatic arthritis. Collectively, our results obtained in a Serbian cohort expand current knowledge regarding individual predisposition to psoriatic disease.(Ann Dermatol 27(2) 128∼132, 2015)
TNF, IL12B, and IFNG Gene Polymorphisms in Serbian Patients with Psoriasis
( Svetlana Popadic ),( Emina Savic ),( Milos Markovic ),( Zorica Ramic ),( Ljiljana Medenica ),( Vera Pravica ),( Zorica Spuran ),( Vladimir Trajkovic ),( Dusan Popadic ) 대한피부과학회 2015 Annals of Dermatology Vol.27 No.3
Background: Psoriasis is a common chronic inflammatory skin disease with a strong genetic basis. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) such are IL-12 and IL-23, and interferon gamma (IFN-γ) are released from various inflammatory and resident cells, and have been implicated in the initiation/maintenance of inflammation. Certain alleles of the aforementioned cytokines may be associated with disease susceptibility/severity. Objective: To investigate the association of three common functional gene polymorphisms, namely TNF -308 G/A (rs1800629), IL12B (encoding the p40 subunit of IL-12/23) +1188 A/C (rs3212227), and IFNG +874 T/A (rs2430561) with psoriasis development and severity in Serbian patients. Methods: We genotyped 130 patients with psoriasis (26 of whom also had psoriatic arthritis) and 259 controls; rs1800629 and rs3212227, and rs2430561, by real-time PCR assay. Results: The TNF GG genotype was detected at a higher frequency in patients with psoriasis compared to control subjects (OR, 1.420; 95% CI, 0.870∼2.403) without statistical significance (p= 0.191). Lack of the TNF G allele was associated with lower psoriasis severity (p=0.007). The IL12B AC genotype was underrepresented in the patients with psoriatic arthritis compared to healthy subjects (OR, 0.308; 95% CI, 0.090∼ 1.057; p=0.049). The distribution of the rs2430561 allele and genotype frequencies was similar between patients with psoriasis and controls. Conclusion: Our study demonstrates an effect of the rs1800629 on psoriasis severity, and a marginal impact of the rs3212227 on susceptibility to psoriatic arthritis. Collectively, our results obtained in a Serbian cohort expand current knowledge regarding individual predisposition to psoriatic disease. (Ann Dermatol 27(2) 128∼132, 2015)
Pejnovic, N.,Vratimos, A.,Lee, S.H.,Popadic, D.,Takeda, K.,Akira, S.,Chan, W.L. Pergamon Press 2009 Molecular immunology Vol.47 No.1
Recent reports show T helper 17 (Th17) cells are involved in the pathogenesis of various chronic inflammatory diseases formerly categorized as Th1-mediated disorders. Interleukin-18 (IL-18) induces Th1 cells to produce interferon-γ (IFN-γ) which is proatherogenic, while cholesterol causes atherosclerosis and stimulates intact rat aortae to produce prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), a strong regulator of IL-23 that expands Th17. We wanted to test whether Th17 is proatherogenic and whether cholesterol can induce the alternative Th17 pathway in IL-18 deficient apolipoprotein E-knockout (ApoE<SUP>-/-</SUP>) mice that have reduced Th1 cells, if they are fed high-cholesterol diet. IL-18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> and IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice aged 5 weeks were fed high-cholesterol diet (HCD) and control littermates of IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> low-cholesterol diet (LCD) for 12 weeks. At termination, cryosectioned aortic arches were stained for lesion measurement and immunohistochemistry. We found that serum cholesterol and triglyceride levels were significantly higher in IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice on HCD and they also had significantly increased atherosclerosis compared with 18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> mice or IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice on LCD. Increased atherosclerosis correlates with enhanced Th17-cells, IL-23-producing vascular smooth muscle cells (VSMC) and macrophages, and thin fibrous cap in lesions, the morphology indicative of unstable plaques prone to rupture. In vitro, cholesterol significantly enhances VSMCs explanted from IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> but not IL-18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> aorta to produce IL-23 and homocysteine mediates secretion. This study suggests that in IL-18 deficiency, cholesterol in HCD synergize mechanistically with homocysteine to accelerate atherosclerosis via the alternative IL-23/Th17 pathway, demonstrating a new role for Th17 in atherosclerosis.
Aleksandra Petrovic,Nebojsa Cvetkovic,Dragica Popadic,Radmila Popovic,Svetlana Ibric,Svetlana Trajkovic,Zorica Djuric 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.12
Using mixture experimental design, the effect of carbomer (Carbopol® 971P NF) and hydroxypropylmethylcellulose (Methocel® K100M or Methocel® K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.
Aleksandra Petrovic,Svetlana Ibric,Svetlana Trajkovic,Radmila Popovic,Zorica Djuric,Dragica Popadic 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.7
The purpose of this study was to investigate the effect of various in vitro test conditions, on the release properties of theophylline (TP) from aminophylline (AP) matrices based on different hydroxypropylmethylcellulose (HPMC) ratio and viscosity grades. The General full factorial experimental design 3 × 3 × 3 was used, based on three independent variables: applied in vitro test (X1), HPMC/drug ratio (X2) and polymer viscosity grade (X3). The drug release percent at 2h (Y2h), 4h (Y4h) and 8 h (Y8h) and time for 50% of TP release from matrices (YT50%) were response variables. Three in vitro tests were used: Test 1 and Test 4 (Theophylline Extended-release Capsules, USP 30) and Half-change method. According to factorial design analyses, in vitro test was the most significant factor influencing mechanism and amount of drug release. For Half Change method erosion was the predominant mechanism indicating Case – II transport, while for Test 1 the release mechanism were followed by both diffusion and erosion. The lowest release exponent n values, obtained from Ritger-Pepass equation, for Test 4 indicate diffusion process inclining from Fickian diffusion to Anomalous transport. Therefore, it is in the stage of development, useful to consider the influence of various in vitro test conditions on the formulation, in order to choose an optimal test for the purpose of future drug release examination.