Background/Aims: This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). Methods: A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. Results: A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients. Conclusions ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Patients on dialysis have numerous gastrointestinal problems related to uremia, which may represent concealed cholecystitis. We investigated the incidence and risk of acute cholecystitis in dialysis patients and used national health insurance data to identify acute cholecystitis in Korea. Methods: The Korean National Health Insurance Database was used, with excerpted data from the insurance claim of the International Classification of Diseases code of dialysis and acute cholecystitis treated with cholecystectomy. We included all patients who commenced dialysis between 2004 and 2013 and selected the same number of controls via propensity score matching. Results: A total of 59,999 dialysis and control patients were analyzed; of these, 3,940 dialysis patients (6.6%) and 647 controls (1.1%) developed acute cholecystitis. The overall incidence of acute cholecystitis was 8.04-fold higher in dialysis patients than in controls (95% confidence interval, 7.40–8.76). The acute cholecystitis incidence rate (incidence rate ratio, 23.13) was especially high in the oldest group of dialysis patients (aged ≥80 years) compared with that of controls. Dialysis was a significant risk factor for acute cholecystitis (adjusted hazard ratio, 8.94; 95% confidence interval, 8.19–9.76). Acute cholecystitis developed in 3,558 of 54,103 hemodialysis patients (6.6%) and in 382 of 5,896 patients (6.5%) undergoing peritoneal dialysis. Conclusion: Patients undergoing dialysis had a higher incidence and risk of acute cholecystitis than the general population. The possibility of a gallbladder disorder developing in patients with gastrointestinal problems should be considered in the dialysis clinic.

Differences in responsiveness of BALB/c substrains have been investigated in various fields, including diabetes induction, corpus callosum deficiency, virus-induced demyelinating disease, aggressive behavior and osteonecrosis. However, induction efficacy of skin tumor remains untried. We therefore investigated the influence of BALB/c substrain backgrounds on the skin tumor induction efficacy in response to DMBA (7,12-Dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoylphorbol-13-acetate) cotreatment. Alterations in the levels of tumor growth related factors, histopathological structure, and the expression to tumor related proteins were measured in three BALB/c substrains (BALB/cKorl, BALB/cA and BALB/cB) after exposure to DMBA (25 μg/kg) and three different doses of TPA (2, 4 and 8 μg/kg). The average number and induction efficacy of tumors in response to DMBA+TPA treatment were significantly greater in the BALB/cKorl substrain than in BALB/cA and BALB/cB. However, cotreatment with DMBA+TPA induced similar responses for body and organ weights of all three substrains. Few differences were detected in the serum analyzing factors, while similar responsiveness was observed for blood analyzing factors after DMBA+TPA treatment. Furthermore, the three BALB/c substrains exhibited similar patterns in their histopathological structure in DMBA+TPA-induced tumors. The expression levels of apoptotic proteins and tumor related proteins were constantly maintained in all three BALB/c substrains treated with DMBA+TPA. In addition, the responsiveness to cisplatin treatment was overall very similar in the three BALB/c substrains with DMBA+TPA-induced tumors. Taken together, these results indicate that genetic background of the three BALB/c substrains does not have a major effect on the DMBA+TPA-induced skin carcinogenesis and therapeutic responsiveness of cisplatin, except induction efficacy.

In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model.
Animals ; Caspase 3 ; Cell Proliferation ; Cisplatin ; Immunotherapy ; Interleukin-10 ; Interleukin-6 ; Korea ; Lung ; Mice ; Models, Animal ; Molecular Biology ; Neoplasm Metastasis ; Tumor Suppressor Protein p53 ; Vascular Endothelial Growth Factor A

BACKGROUND AND OBJECTIVES: Manuka honey has anti-microbial, anti-inflammatory, and anti-proliferative action with a high concentration of methylglyoxal compound. It is also effective in killing Staphylococcus aureus biofilm and effective for the acute exacerbation of chronic rhinosinusitis. The aim of this study was to determine the anti-fibrotic effect of manuka honey in nasal polyp fibroblasts. MATERIALS AND METHOD: Primary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). To determine the anti-fibrotic effect of manuka honey, fibroblasts were pre-treated with various concentration of the honey. Reverse transcription-polymerase chain reaction and western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), collagen type I, and matrix metalloproteinase-9 (MMP-9) messenger ribonucleic acid (mRNA) expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad (pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were then determined by western blotting. RESULTS: TGF-β1 stimulation increased α-SMA, collagen type I, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Manuka honey effectively suppressed α-SMA, collagen type I, and MMP-9 mRNA expression and protein production. Its inhibitory role on TGF-β1 induced myofibroblast differentiation and its extracellular matrix production was associated with Smad2/3 and AMPK pathway. CONCLUSION: Manuka honey can inhibit TGF-β1 induced myofibroblast differentiation, collagen type I, and MMP-9 production in nasal fibroblasts. These results suggest that manuka honey might be a useful candidate for the inhibition of nasal polyp formation if further studies in vivo were accompanied.
Actins ; Adenosine ; AMP-Activated Protein Kinases ; Biofilms ; Blotting, Western ; Collagen Type I ; Extracellular Matrix ; Fibroblasts ; Homicide ; Honey ; Matrix Metalloproteinase 9 ; Methods ; Myofibroblasts ; Nasal Polyps ; Protein Kinases ; Pyruvaldehyde ; RNA ; RNA, Messenger ; Staphylococcus aureus ; Transforming Growth Factor beta ; Transforming Growth Factors

BACKGROUND AND OBJECTIVES: Manuka honey has anti-microbial, anti-inflammatory, and anti-proliferative action with a high concentration of methylglyoxal compound. It is also effective in killing Staphylococcus aureus biofilm and effective for the acute exacerbation of chronic rhinosinusitis. The aim of this study was to determine the anti-fibrotic effect of manuka honey in nasal polyp fibroblasts.MATERIALS AND METHOD: Primary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). To determine the anti-fibrotic effect of manuka honey, fibroblasts were pre-treated with various concentration of the honey. Reverse transcription-polymerase chain reaction and western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), collagen type I, and matrix metalloproteinase-9 (MMP-9) messenger ribonucleic acid (mRNA) expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad (pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were then determined by western blotting. RESULTS: TGF-β1 stimulation increased α-SMA, collagen type I, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Manuka honey effectively suppressed α-SMA, collagen type I, and MMP-9 mRNA expression and protein production. Its inhibitory role on TGF-β1 induced myofibroblast differentiation and its extracellular matrix production was associated with Smad2/3 and AMPK pathway. CONCLUSION Manuka honey can inhibit TGF-β1 induced myofibroblast differentiation, collagen type I, and MMP-9 production in nasal fibroblasts. These results suggest that manuka honey might be a useful candidate for the inhibition of nasal polyp formation if further studies in vivo were accompanied.

Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.
Acetylcholinesterase ; Animals ; Brain Diseases ; Cognition Disorders* ; Cytokines ; DNA Nucleotidylexotransferase ; Humans ; Learning ; Memory ; Mice ; Mice, Inbred ICR ; Neurons ; Oxidative Stress ; Scopolamine Hydrobromide ; Superoxide Dismutase ; United Nations ; Water