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Background@#Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. @*Methods@#Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer CellFree Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. @*Results@#Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. @*Conclusions@#Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.
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Background@#The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. @*Methods@#We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea.Obesity was defined as a body mass index value of ≥ 30 kg/m 2 . @*Results@#The most common disease was IgA nephropathy (IgAN) in both obese and nonobese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37–2.17; OR, 1.96, 95% CI, 1.21–3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62–0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01–2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36–8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09–5.64). @*Conclusion@#Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.
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Purpose@#With the revision of the Organ and Transplantation Act in 2018, the hand has become legal as an area of transplantable organs in Korea. In January 2021, the first hand allotransplantation since legalization was successfully performed, and we have performed a total of three successful hand transplantation since then. By comparing and incorporating our experiences, this study aimed to provide a comprehensive reconstructive solution for hand amputation in Korea. @*Materials and Methods@#Recipients were selected through a structured preoperative evaluation, and hand transplantations were performed at the distal forearm level. Postoperatively, patients were treated with three-drug immunosuppressive regimen, and functional outcomes were monitored. @*Results@#The hand transplantations were performed without intraoperative complications. All patients had partial skin necrosis and underwent additional surgical procedures in 2 months after transplantation. After additional operations, no further severe complications were observed. Also, patients developed acute rejection within 3 months of surgery, but all resolved within 2 weeks after steroid pulse therapy. Motor and sensory function improved dramatically, and patients were very satisfied with the appearance and function of their transplanted hands. @*Conclusion@#Hand transplantation is a viable reconstructive option, and patients have shown positive functional and psychological outcomes. Although this study has limitations, such as the small number of patients and short follow-up period, we should focus on continued recovery of hand function, and be careful not to develop side effects from immunosuppressive drugs. Through the present study, we will continue to strive for a bright future regarding hand transplantation in Korea.
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Purpose@#We aimed to identify the risk factors for salvage procedure (SP) required for refractory adenomatous tissue resistant to morcellation during holmium laser enucleation of the prostate (HoLEP). @*Methods@#Patients who underwent HoLEP between January 2010 and April 2020 at Seoul National University Hospital were analyzed. SPs were defined as cases of conversion to resection of the prostatic tissue using an electrosurgical loop after morcellation or secondary morcellation a few days after surgery or conversion to open cystotomy. @*Results@#Among a total of 2,427 patients, 260 were identified as having SP (SP group) (transurethral resection-nodule [n = 250, 96.1%], secondary morcellation a few days after surgery [n = 9, 3.5%], and conversion to open cystotomy [n = 1, 0.4%]). Patients in the SP group were older and had higher 5-α reductase inhibitors use, higher prostate-specific antigen, larger total prostate volume, and larger transition zone volume (TZV) than those in the non-SP group. In the multivariable logistic regression analysis, only age and TZV were associated with SP. Compared to 40s and 50s, the odds ratios (ORs) were 3.84 in 60s (95% confidence interval [CI] 1.37–10.78, P = 0.011), 4.53 in 70s (95% CI, 1.62–12.62, P = 0.004), and 6.59 in 80s or older (95% CI, 2.23–19.46, P = 0.001). The ORs of the SP were analyzed per TZV quartile. Compared to TZV ≤ 20.3 mL, the OR was 3.75 in 32.0 mL 60 years or those with TZV > 32 mL. In order to more efficiently remove these resistant adenomas, it is necessary to develop more efficient morcellators in the future.
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Background@#The gut–brain axis (GBA) in Parkinson’s disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. @*Results@#The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSEhαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. @*Conclusions@#The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.
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Purpose@#The purpose of this study was to identify factors that can affect transition shock in newly-graduated nurses. @*Methods@#The first descriptive written survey was conducted on 450 graduate students from five nursing colleges. After their employment, the second survey was conducted on 316 participants who had responded to the first survey. A total of 158 respondents were used for the final analysis. Data were analyzed using an independent t-test, ANOVA, Tukey test, Pearson’s correlation coefficient, and hierarchical multiple regression analysis with the SPSS Win 25.0 Program. @*Results@#The average age of the participants was 24.25±4.47. Of the participants, 126 (79.8%) were satisfied that they had majored in nursing. The average score for transition shock was 2.61±0.55 points. Factors influencing the transition shock of newly-graduated nurses were the working department, working period, and working environment. The more positively the newly-graduated nurses perceived the nursing work environment, the less of a transition shock they experienced. Grade point average, clinical competence, confidence in performing core nursing skills, and nursing professionalism did not affect their transition shock. It could be confirmed that there is a gap between college nursing education and the clinical field. @*Conclusion@#In order to reduce the transition shock of newly-graduated nurses, it is necessary to improve the nursing work environment and apply educational and emotional support strategies according to the characteristics of each work department and the period of work.
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Purpose@#DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. @*Methods@#This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. @*Results@#In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. @*Conclusions@#Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.
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Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis.Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive.Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.
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Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. Methods: This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results: Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. Conclusion: Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed.
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Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients. Methods: Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation. Results: Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/ mm2 vs. 194/mm2 , p < 0.05). Conclusion: Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.
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Purpose@#Advances in the diagnosis and treatment of prostate cancer have increased the patients’ stress level and decreased the quality of life. A variety of instruments are currently available to evaluate patients with prostate cancer. However, only a few tools are available to assess Korean patients, and therefore we demonstrated a linguistic validation of Korean Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). @*Methods@#EPIC-CP was translated into Korean and the linguistic validation was evaluated. The evaluation process includes permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two bilingual translators independently translated the original questionnaire, discussed the feasibility and naturalness of initial translation, followed by revision to the reconciled version. Another translator then performed a backward translation into English. Ten patients with prostate cancer completed the translated questionnaire and performed cognitive debriefing. @*Results@#The original EPIC-CP was translated into 2 Korean versions. The different wording in both versions and the ordinary words in the initial translations were changed considering the nuances and meanings of medical terms. During the backward translation, the panels made slight changes to clarify the meaning and nuances of the translated questionnaire. During cognitive debriefing, 10 patients answered the questionnaire and offered their opinions regarding comprehensibility and naturalness. Most patients agreed that the translation was comprehensible in general. @*Conclusions@#Our study provides a successful linguistic validation of the EPIC-CP questionnaire. The translation is a helpful diagnostic tool to ensure the quality of life of patients with prostate cancer attending crowded clinics.
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Background@#A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. @*Methods@#C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. @*Results@#Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. @*Conclusion@#Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.
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Background@#To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumorrelated proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). @*Results@#Cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with CT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the CT26 tumor. Growth inhibition of CT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (Cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and IL-10, in the CT26 tumors of the three BALB/c substrains. @*Conclusions@#Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the CT26 syngeneic tumor.
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Background@#The aim of this study is to evaluate the postoperative stability of zygomaticomaxillary complex (ZMC) fractures according to the number of fixation sites and to investigate the direction of postoperative displacement of the unfixed part of the fractured segment. @*Methods@#This study was retrospectively performed on 38 patients who were treated by open reduction and internal fixation of ZMC fractures and were taken postoperative computed tomography (CT) between February 2012 and July 2019. The patients were classified into 3 groups: 1-point fixation, 2-point fixation, 3-point fixation according to the number of fixations. The postoperative displacement of the fractured segment was evaluated by the superimposition between postoperative CT and follow-up CT, and the postoperative stability according to the fixation sites was investigated through the amount of postoperative displacement. In addition, it was investigated in which direction the location of the fractured segment was changed in the unfixed fractured segment according to the fixation sites. @*Results@#The amount of postoperative displacement of the fractured segment was 0.75 ± 1.18 mm on average. In the postoperative displacement of the distal area according to the number of fixation of the fracture, there was no statistically significant difference in the amount of displacement of the fracture (p = 0.574). As for the direction of the change in the location of the fractured segment, 12 patients among 38 patients with the change in the location of the fractured segment were investigated, and the displacement in the medial direction (n = 11, 91.67%) was the most common in all three fixation methods. @*Conclusion@#In patients with a ZMC fracture who were treated by open reduction and internal fixation, the number of fixations did not make the difference in the postoperative displacement of the fracture. In addition, the fractured segment mainly changes in the medial direction after surgery, and this fact can be used as a reference for the reduction direction during surgery for the stable prognosis.
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Background@#To investigate the clinical and microbiological features of febrile patients with upper urinary tract calculi and factors that affect empirical antibiotic resistance. @*Methods@#A retrospective analysis was performed on 203 febrile patients hospitalized between January 2011 and December 2016 with antibiotic treatment for urinary tract infections and upper urinary tract calculi at three institutions. We collected and analyzed data, including patients' age, sex, body mass index, underlying diseases, stone-related factors, and the results of urine and blood culture examinations and antibiotic sensitivity tests. @*Results@#The male-to-female ratio was 1:2.3. Bacteria were identified in 152 of the 203 patients (74.9%). The most commonly cultured microorganisms included Escherichia coli (44.1%), followed by Enterococci spp. (11.8%), Proteus spp. (8.6%), Streptococcus agalactiae (6.6%), Klebsiella spp. (5.3%), Pseudomonas spp. (4.6%), coagulase-negative Staphylococcus (4.0%), Staphylococcus epidermidis (4.0%), Serratia spp. (2.6%), Enterobacter spp. (0.7%), Acinetobacter spp. (0.7%), and mixed infections (7.2%). Cultured bacterial species showed sex-specific differences. Multivariate analysis revealed that calculi's multiplicity was an independent predictive factor for quinolone resistance (P = 0.008). Recurrent infections were a significant predictor of cefotaxime resistance during multivariable analysis (P = 0.041). @*Conclusion@#Based on the present study results, quinolone was not recommended as the empirical treatment in febrile patients with upper urinary tract calculi. Combination antibiotic therapy is recommended in cases of recurrent infections due to the possible occurrence of cefotaxime resistance.
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Background@#Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. @*Results@#Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. @*Conclusions@#These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.
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Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.
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Background@#As a laboratory animal resource, the ICR mouse is commonly used in a variety of research fields. However, information on differences in exercise-related characteristics in ICR mice derived from different lineages and the underlying mechanisms remains to be elucidated. In this study, we investigated the intrinsic exercise capacity and a magnitude of response to acute exercise, and sought to identify mechanisms contributing to difference in Korl:ICR (a novel ICR lineage recently established by the National Institute of Food and Drug Safety Evaluation, Korea) and two commercialized ICR lineages derived from different origins (viz., A:ICR mouse from Orient Bio Com, the United States, and B:ICR mouse from Japan SLC Inc., Japan). @*Results@#Results showed that despite no significant difference in body weight and weight-proportioned tissue mass of heart and skeletal muscles among groups, the relatively low intrinsic exercise capacity and exaggerated response to acute exercise were identified in B:ICR comparted with Korl:ICR and A:ICR, as reflected by total work and lactate threshold (LT). Also, the mitochondrial efficiency expressed as the complex 1 and complex 1 + 2 respiratory control ratio (RCR) values for cardiac mitochondrial O 2 consumption in B:ICR was significantly lower than that in Korl:ICR with higher level of state 2 respiration by glutamate/malate and UCP3 expression in cardiac muscle. @*Conclusions@#Taken together, these results indicate that the intrinsic exercise capacity of ICR mouse varies according to lineages, suggesting the role of cardiac mitochondrial coupling efficiency as a possible mechanism that might contribute to differences in the intrinsic exercise capacity and magnitude of response to exercise.
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Background@#Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. @*Results@#Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. @*Conclusions@#These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.
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Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.