• 대한한방내과학회지
• /
• 제24권1호
• /
• pp.75-83
• /
• 2003

Objectives : Peroxynitrite($ONOO^-$), formed from the reaction of $O2^-$ and NO, is a cytotoxic species that can oxidize several cellular components such as proteins, lipids and DNA. It has been involved in the aging process and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate scavenging activities of $ONOO^-$ and its precursors, NO and $O_{2^-}$ and its scavenging mechanism of Zingiberis Rhizoma (ZR). Methods : To investigate scavenging activities of $ONOO^-,\;NO,\;O_{2^-}$ and its scavenging mechanism, we used fluorescent probes like DCFDA, DAF-2 and DHR 123. The $ONOO^-$ scavenging activity on ZR was assayed by measuring oxidized dihydrorhodamine 123 (DHR 123) by fluorometry. The scavenging efficacy was expressed as IC50, showing the concentration of each sample that is required to cause 50% inhibition of DHR 123 oxidation. In a separate study, the protective effect of ZR on $ONOO^-$-induced nitration of bovine serum albumin was investigated through immuno-assay with a monoclonal anti-nitryrosine antibody, and a horseradish peroxidase-conjugated anti-mouse secondary antibody from sheep. Results : ZR markedly scavenged authentic $ONOO^-,\;O_{2^-}$ and NO. It also inhibited $ONOO^-$ induced by $O_{2^-}$ and NO which are derived from SIN-1. The data demonstrated that ZR led to decreased $ONOO^-$ mediated nitration of tyrosine through electron donation. It also inhibited the nitration of bovine serum albumin induced by $ONOO^-$ in a dose-dependent manner. Furtheremore, it blocked LPS-induced ROS and RNS generation. Conclusions : These results suggest that ZR can be developed as an effective $ONOO^-$ scavenger for the prevention of aging process and age-related diseases.

• Biomolecules & Therapeutics
• /
• 제19권1호
• /
• pp.70-76
• /
• 2011

Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-$\kappa}B$. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.

• Biomolecules & Therapeutics
• /
• 제28권4호
• /
• pp.361-369
• /
• 2020

Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

• 생약학회지
• /
• 제36권4호통권143호
• /
• pp.311-317
• /
• 2005

GCSB-5 is a purified extract from a mixture of 6 Oriental herbs (Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex) that have been widely used for the treatment of inflammatory diseases in the East Asia. The aim of this study was to investigate the anti-inflammatory potential of GCSB-5. The animals used in this study were administered either vehicle or GCSB-5 (30, 100, 300, and 600 mg/kg) orally. The GCSB-5 significantly inhibited the increased of acetic acid-induced vascular permeability (30.9%-34.2% inhibition at 30-300 mg/kg). The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by GCSB-5 in doses of 100, 300, and 600 mg/kg. Maximal inhibition (50.9%) was obtained with GCSB-5 at dose of 300 mg/kg. However, it did not have any anti-inflammatory action in the rheumatoid arthritis induced by Freund's complete adjuvant or in the granuloma induced by carrageenan. Our finding suggest that GCSB-5 has a anti-inflammatory activity.

• Archives of Plastic Surgery
• /
• 제32권1호
• /
• pp.93-99
• /
• 2005

In spite of proper maneuver of total knee replacement arthroplasty, some patients suffer from skin necrosis just above the implant. From Mar. 2000 to Jan. 2004, the authors performed reconstruction of knee skin defects after total knee replacement athroplasty. Total 6 cases of flap surgery were performed and patients ranged between 43-years-old to 82-years-old. Rectus femoris perforator based reversed adipofascial flaps were used in 2 cases, medial gastrocnemius muscular island flaps were used in 2 cases and sural artery based on adipofascial rotation flap was used in 1 case. One patient with extended necrosis underwent reconstruction with dual flaps of sural artery based adipofascial rotation flap and medial gastrocnemius muscular island flap. There were no distinctive complication needing additional procedure in all cases during the long term follow up. Reconstruction of necrosis following total knee replacement arthroplasty had several characteristics different from simple knee defect. The patients might have the history of long term steroid usages, excessive skin tension due to implants, underlying disease such as diabetes, rheumatoid disease, and etc. In addition, the early ambulation is mandatory in these patients of total knee replacement arthroplasty. With regards to these special considerations, a single stage and reliable operation must be needed. The authors introduce various reconstruction methods and algorithm that may aid easy decision making.

• Archives of Plastic Surgery
• /
• 제33권1호
• /
• pp.120-123
• /
• 2006

Spontaneous extensor pollicis longus tendon rupture is commonly caused by attrition of the tendon from trauma or inflammatory processes. We experienced a patient with extensor pollicis longus tendon rupture after steroid injection, in which the rupture may have been caused by the effects of steroid itself as well as direct damage from the needle. A 51-year-old woman complained of inability to extend her right thumb at the first metacarpophalangal & interphalangeal joint level. The patient had a history of local steroid injection into the dorsal & radial side of wrist on two occations, and had no history of trauma or rheumatologic disease. After a physical examination of the patient, we decided to explore the wrist. The patient agreed with operation. Intraoperatively, an incision was made into the wrist and the proximal and distal ends of the ruptured extensor pollicis longus tendon were identified. The defect between the proximal and the distal end was measured to approach 8cm, and a palmaris longus tendon graft was performed. After three months of rehabilitation, the first metacarpophalangal & interphalangeal joint recovered the normal range of motion. Steroid injection has been widely used in various musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis. However, inadvertent steroid injection into the extra or intra articular spaces may lead to tendon rupture. Steroids reduce tensile strength by decreasing tenocyte activity and collagen synthesis. Also, the physical effect of direct needle-stick injury into the mesotenon and blood vessels around the tendon may cause damage. In addition, hematoma and edema may increase pressure around the tendon and compromise blood supply, leading to tendon degeneration and subsequent rupture. When injecting steroid into an articular area, all physicians should have a complete understanding of the surrounding anatomy and always keep in mind the hazards of such procedures.

• 대한미생물학회지
• /
• 제21권2호
• /
• pp.171-179
• /
• 1986

The HLA class II region encodes a series of polymorphic glycoproteins that form cell surface heterodimers each consisting of one $\alpha$ and one $\beta$ chain. Thess class II molecules are encoded by genes clustered within three loci. DP, DQ, and DR are functfonally implicated as regulatory signals in intercellular communication during the immune resposes. The phenotypic hallmark of the HLA complex is a high degree of structural and functional polymorphism. Detailed analysis. of such polymorphisms should aid in understanding the molecular basis for associations between HLA and diseases. We have used techniques of restriction enzyme fragment analysis by Southern blotting to investigate polymorphisms associated with DQ $\beta$ class II genes on haplotypes expressing the HLA-DR4 and -DQw3 specificities. The endonucleases Hind III and Bam HI were used to identify a specific DQ $\beta$ genomic polymorphism that precisely corrresponds with the reactivity of a monoclonal antibody A-10-83, previously shown to define a serologic split of DQw3. This study identifies two allelic DQ va. riants. DQw3.1 and DQw3.2. We used these specific genotypic markers to investigate the genomic basis of the association of DR4 with insulin-dependent diabetes mellitus(IDDM) and seropositive juvenile rheumatoid arthritis(JRA). The DR4 positive IDDM demonstrate the predominant expression of DQw3.2 and the very rare expression of DQw3.l. However, in haplotype matched siblings from two IDDM families, all of the DR4 positive siblings display a IDDM-associated DQw3.2 allele. Thus, both affected and healthy individuals can carry the same haplotypes and genomic markers, demonstrating that thess specific allelic variants are genetic elements that indicate a increased risk of IDDM but are not in fact disease specific. We contrasted this result with a similar analysis of patients with another DR4-associated disease, JRA. In contrast to the preponderance of the DQw3.2 allele in IDDM, the JRA patients expressed either the DQw3.1 or the DQw3.2 allele and sometimes both, without apparent association with disease expession. The different genomic markers reported here within HLA-DQ region potentially an analysis of HLA-associated function and disease susceptibility.

• 한국축산식품학회:학술대회논문집
• /
• 한국축산식품학회 2006년도 정기총회 및 제37차 춘계 국제학술발표대회
• /
• pp.122-127
• /
• 2006

The innermost structures of synovium consist of one to three layers of cells generally identified as synovial lining cells(SLC). The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial(FLS) cells derived from the synovia of rheumatoid arthritis. Post-traumatic arthritis(PTA) is one of the most common causes of secondary osteoarthritis, and usually affects younger people. The proteins were separated by two-dimensional polyacrylamide gel electrophoresis and RNA expression investigated by RT-PCR Proteome analyses led to the identification of more than 1,500 protein spots and of 11 differently expressed protein spots among them. Six proteins were down-regulated, and five proteins were up-regulated in ACL-transected synovial tissue. Among these, spots 3 and 8 were identified as cofilin-1 and smooth muscle protein $22-\alpha$, respectively, Therefore, the proteome analysis of synovial tissue is a useful approach to investigate a joint after an injury and can be used to understand the pathogenesis of PTA.

• 생약학회지
• /
• 제49권2호
• /
• pp.145-154
• /
• 2018

Aconiti Kusnezoffii Tuber has been traditionally used to treat the symptoms of rheumatoid arthritis and joint pain. The main constituents are diterpenoid alkaloids such as benzoylmesaconine, benzoylaconine, mesaconitine, aconitine, and hypaconitine. In Korea, Aconiti Kusnezoffii Tuber is officially defined as the tubers of Aconitum kusnezoffii Reichb., A. ciliare Decasisne, and A. triphyllum Nakai. On the other hand, only the tuber of A. kusnezoffii is to be used in China. In order to identify the botanical origin of Aconiti Kusnezoffii Tuber circulated in Korea, we analyzed 24 samples of Aconiti Kusnezoffii Tuber obtained from local markets for comparative DNA analysis. The sequence analysis of nrRNA ITS 1 was useful to distinguish Aconitum species and revealed that the roots of A. karakolicum were circulated in Korean markets without discretion. HPLC quantitative analysis showed that aconitine was detected at the highest amount in A. karakolicum. Authentic diterpenoid alkaloids were coinjected for quantification of aconitine-type ingredients. All data were statistically grouped by Principal Component Analysis (PCA). This study suggests that both molecular and chemical analyses should be utilized for the standardization and the quality control for Aconiti Kusnezoffii Tuber.

• 동의생리병리학회지
• /
• 제19권5호
• /
• pp.1225-1232
• /
• 2005

Based on traditional medicine theories, GC, an extract from 5 herbs, has been formulated and prescribed for the treatment of human rheumatoid arthritis(hRA) for many years. The present studies was done to investigate whether GC has inhibitory effects on activation of fibroblast-like sinoviocytes isolated from a RA patient. In tumor necrosis factor-${\alpha}(TNF-{\alpha}$)/ interleukin-IL-$1{\beta}$(IL-$1{\beta}$) treated human sinoviocytes, the mRNA expression of molecular indicators related to pathologic changes of the sinoviocytes were examined using quantitative real-time PCR. The treatment of GC($10{\mu}g/ml$) significantly suppressed the expression of proinflammatory cytokines and chemokines such as $TNF-{\alpha}$, IL-6 and IL-8 compared with the control, but not $IL-1{\beta}$, The mRNA level of intracellular adhesion molecule-1 (ICAM-1) which is known to increase in the activated sinoviocytes of RA patients, was slightly decreased by GC. The expression of NOS-II was considerably reduced, which was accompanied by a decrease in the production of nitric oxide(NO). Furthermore, GC dramatically raised the mRNA levels of tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), while those of matrix metalloproteinase-3 were significantly lowered. Taken together, these data suggested that GC might suppress the activation of sinoviocytes in hRA.