PURPOSE: Leptin may play an important role in the pathophysiology of osteoarthritis. However, the effect of letpin on the anabolic and catabolic metabolisms in chondrocytes remains unclearly elucidated. Therefore, the purpose of this study was to investigate the effect of leptin on proliferation, anabolic and catabolic metabolism of chondrocyte using ATDC5 chondrogenic cell line. MATERIALS AND METHODS: The effects of leptin on chodnrocyte proliferation, anabolic and catabolic meatabolism were examined in ATDC5 cells treated with leptin at varying concentrations(10, 100, 300, 600 ng/ml) for 24, 48, and 72 hours. The cell proliferation was evaluated by MTT assay. The anabolic and catabolic activities were assayed by RT-PCR for transforming growth factor-beta(TNF-alpha), proteoglycan-4 (PRG4), type- I collagen (type- I Col) and tumor necrosis factor-beta(TNF-alpha), matrix metalloproteinase -2 (MMP-2), respectively. RESULTS: Leptin treatment did not influence cell proliferation of chondrocyte regardless of concentration. TGF-beta expression was increased until 48 hours of leptin treatment compared to controls. Especially, it was significantly increased in leptin of 10 ng/ml and 100 ng/ml (P<0.05). PRG4 expression was not different between letpin treatment and controls. Type-I Col expression was decreased in dose- and time-dependent manner. Leptin of 10ng/ml significantly inhibited MMP-2 and TNF-alpha expressions compared to controls (P<0.05). CONCLUSION: This study shows that leptin at low concentration increases TGF-beta expression, but inhibits the expression of TNF-alpha and MMP-2. Also this study shows that leptin do not affect the cell proliferation of chondrocytes. These results suggest that leptin at low or physiological level contributes to the prevention of cartilage damage by stimulating anabolic activity and inhibiting catabolic activity of chondrocyte rather than chondrocyte regeneration by increasing cell proliferation.
Cartilage ; Cell Proliferation ; Chondrocytes ; Collagen ; Leptin ; Necrosis ; Osteoarthritis ; Regeneration ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

BACKGROUND/AIMS: Hyperglycemia is associated with decreased 2-18[F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumors assessed by positron emission tomography (PET). In this retrospective study we investigated a comparison of standardized uptake values (SUVs) in patients with primary colorectal cancers who either had diabetes mellitus (DM) or were otherwise healthy. METHODS: The medical records of 397 patients who were diagnosed with colorectal cancer and underwent PET-CT between January 2006 and December 2012 were analyzed. Eighty patients with DM and 317 patients without DM were included. Clinical characteristics were reviewed and maximal standardized uptake values (SUVmax) were calculated in the primary colorectal lesions. RESULTS: There was no significant difference between tumor SUVmax in DM patients (10.60+/-5.78) and those without DM (10.92+/-5.44). In addition, no significant difference was detected between tumor SUVmax in DM patients with glycated hemoglobin (HbA1c) levels <8% (10.34+/-5.17) and those with HbA1c levels > or =8% (10.61+/-7.27). The maximum size of the primary colorectal tumor was associated with SUVmax in a linear regression analysis. CONCLUSION: The results of this study showed that DM did not influence FDG uptake values in colorectal cancer patients regardless of glucose levels.
Colorectal Neoplasms* ; Diabetes Mellitus* ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Linear Models ; Medical Records ; Positron-Emission Tomography* ; Retrospective Studies

PURPOSE: Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. RESULTS: SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. N(G)-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. CONCLUSION: These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; Acetylcholine ; Arginase* ; Arginine ; Blotting, Western ; Endothelium ; Human Umbilical Vein Endothelial Cells ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase Type III* ; Oxidation-Reduction ; Peroxynitrous Acid ; Phosphorylation* ; Reactive Oxygen Species

Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-theta (PKCtheta) and protein kinase C-beta (PKCbeta) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCtheta and PKCbeta stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox-/- mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.
Animals ; Aorta/*cytology ; Cell Line ; Cell Proliferation ; Cells, Cultured ; Humans ; Lipoproteins, LDL/*metabolism ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinases/metabolism ; Muscle, Smooth, Vascular/cytology ; Myocytes, Smooth Muscle/*cytology ; NADPH Oxidase/*metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Signal Transduction ; Superoxides/metabolism

PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Alleles ; Aspirin ; Asthma ; Cytokines ; Eosinophils ; Haplotypes ; Humans ; Hypersensitivity ; Inflammation ; Ligands ; Logistic Models ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Polymorphism, Single Nucleotide ; PPAR gamma

PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Alleles ; Aspirin ; Asthma ; Cytokines ; Eosinophils ; Haplotypes ; Humans ; Hypersensitivity ; Inflammation ; Ligands ; Logistic Models ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Polymorphism, Single Nucleotide ; PPAR gamma

BACKGROUND: Endoscopic variceal ligation (EVL) has been widely used to control acute variceal bleeding. However, eradication of varices with EVL is difficult and rebleeding following successful EVL is frequently problematic. Our aims were to assess the efficacy of EVL for treatment of acute variceal bleeding and to evaluate risk factors associated with rebleeding during follow-up period. METHODS: One-hundred and five patients were included, who had undergone EVL due to bleeding of esophageal varices. Retrospective analysis was performed about hemostatic success rate, rebleeding rate and risk factors for rebleeding. RESULTS: Hemostatic success rate was 84.8% (89/105). During follow-up period, eradication of varices was observed in 5.7% (6/105), downgrading in 44.8% (47/105), no change of grade in 35.2% (37/105), and progression of varices was observed in 3.8% (4/105). Mean number of sessions for eradication were 3.3 (range, 2 to 8). Rebleeding was observed in 55.2% (58/105), and rebleeding rate increased with lapse of time, as 24.5% after 3 months, and 37.1% in 6 months, and 50.7% in 12 months, respectively. Multivariate analysis for risk factors of rebleeding showed that number of sessions of variceal ligation was associated with significant reduction of rebleeding (p=0.01, OR 0.184). CONCLUSION: EVL was effective for hemostasis of acute variceal bleeding, but progression of varices and rebleeding episodes were common. Adequate follow-up evaluation is mandatory, and repeated variceal ligation is required for eradication of varices and secondary prevention of bleeding.
Esophageal and Gastric Varices* ; Follow-Up Studies ; Hemorrhage ; Hemostasis ; Humans ; Ligation* ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Varicose Veins

No abstract available.

BACKGROUND: Gastric polyp is a descriptive term referring to mucosal prominence that protrudes beyond the flat lining of the stomach. Almost 90% of gastric polyps are hyperplastic polyps. Adenomatous polyps may contain focal carcinomatous foci or undergo carcinomatous changes. It is known that there is some degree of discordance between the results of endoscopic forceps biopsy and pathology of resected specimens. The aim of this study was to investigate the discordance in pathologic findings between endoscopic forceps biopsy and endoscopic resection specimen of gastric polyps. METHODS: We reviewed endoscopic photographs and medical records of the patients who underwent endoscopic resection from April, 1996 through February, 2003. RESULTS: A total of 85 cases of gastric polyps from 74 patients were reviewed. Male-to-female ratio was 1:1.96. Mean age was 59.9+/-10.8 years. Multiple polyps were observed in 10.8%. Gastric polyps occurred in the antrum most frequently (58.8%). Pathology results on resected specimens were as follows: tubular adenoma 45.9%, hyperplastic polyp 31.8%, inflammatory polyp 9.4%, hamartoma 3.5%, fundic gland polyp 2.4%, tubulovillous adenoma 2.4%, adenocarcinoma 2.4%, dysplasia 1.1%, and mucosal pseudolipomatosis 1.1%. Discordance rate between endoscopic biopsy and pathology of resected specimens was 27.1%. There was no relationship between the size of the polyp and concordance rate. CONCLUSIONS: There was considerable discordance in pathologic findings between endoscopic forceps biopsy and resected specimens. Approaches to review the histology of an entire polyp should be performed, especially when an adenoma is suspected.
Adenocarcinoma ; Adenoma ; Adenomatous Polyps ; Biopsy* ; Hamartoma ; Humans ; Medical Records ; Pathology ; Polyps* ; Stomach ; Surgical Instruments*

Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.