Risk Factors of Salvage Procedure for Refractory Morcellation During Holmium Laser Enucleation of the Prostate / 대한배뇨장애요실금학회지

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.

The effect of probiotic supplementation on systemic inflammation in dialysis patients

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.

The effect of periodontitis on recipient outcomes after kidney transplantation

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.

A Case Report of Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination and Heparin Use During Hemodialysis

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.

Factors influencing the transition shock of newly-graduated nurses / 한국간호교육학회지

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.

Efficacy and Safety of DA-8010, a Novel M3 Antagonist, in Patients With Overactive Bladder: A Randomized, Double-Blind Phase 2 Study / 대한배뇨장애요실금학회지

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.

Comparison of intrinsic exercise capacity and response to acute exercise in ICR (Institute of Cancer Research) mice derived from three different lineages / 한국실험동물학회지

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.

Comparison of response to LPS-induced sepsis in three DBA/2 stocks derived from different sources / 한국실험동물학회지

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.

Inflammatory responses of C57BL/6NKorl mice to dextran sulfate sodium-induced colitis: comparison between three C57BL/6N sub-strains / 한국실험동물학회지

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.

Retrospective study about the postoperative stability of zygomaticomaxillary complex fracture / 대한악안면성형재건외과학회지

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.

Comparison of cisplatin-induced anti-tumor response in CT26 syngeneic tumors of three BALB/c substrains / 한국실험동물학회지

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.

Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect

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.

Translation and Linguistic Validation of Korean Version of the Expanded Prostate Cancer Index Composite for Clinical Practice for Patients With Prostate Cancer / 대한배뇨장애요실금학회지

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.

Microbiological Features and Clinical Factors Associated with Empirical Antibiotic Resistance in Febrile Patients with Upper Urinary Tract Calculi

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.

Comparison of intrinsic exercise capacity and response to acute exercise in ICR (Institute of Cancer Research) mice derived from three different lineages / 한국실험동물학회지

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.

Comparison of response to LPS-induced sepsis in three DBA/2 stocks derived from different sources / 한국실험동물학회지

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.

Inflammatory responses of C57BL/6NKorl mice to dextran sulfate sodium-induced colitis: comparison between three C57BL/6N sub-strains / 한국실험동물학회지

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.

Risk factors for postoperative infection of odontogenic cysts associated with mandibular third molar / 대한악안면성형재건외과학회지

Background@#Odontogenic cysts associated with lower third molar are common. The prognosis for surgical treatment is relatively good. However, postoperative infection discourages the clinicians. Hence, we would like to investigate the factors associated with infection after surgical treatment of cysts associated with the mandibular third molar. @*Methods@#We retrospectively reviewed the medical and radiographic records of 81 patients who were diagnosed with dentigerous cyst or odontogenic keratocyst and underwent cyst enucleation. The factors affecting postoperative infection were divided into host factor, treatment factor, and cystic lesion factor. To identify the factors associated with postoperative infection, we attempted to find out the variables with significant differences between the groups with and without infection. @*Results@#A total of 81 patients (64 male and 17 female) were enrolled in this study. There was no statistical relationship about the postoperative infection between all variables (gender, smoking, diabetes mellitus, age, bone grafting, related tooth extraction, previous marsupialization or decompression, type of antibiotics, cortical perforation associated with cystic lesion, preoperative infection, preoperative cyst size). @*Conclusions@#The results of this study suggest that it is not necessary to avoid bone grafts that are concerned about postoperative infection.

Comparative analysis of restraint stress-induced depressive-like phenotypes in C57BL/6N mice derived from three different sources / 한국실험동물학회지

C57BL/6NKorl mice are a novel mouse stock recently developed by the National Institute of Food and Drug Safety Evaluation in Korea. Extensive research into the nature of C57BL/6NKorl mice is being conducted. However, there is no scientific evidence for the phenotypic response to restraint stress (RST), a stress paradigm for modeling depressive disorders, in rodents. In this study, we investigated the repeated RST-induced depressive-like phenotypes in C57BL/6 N mouse substrains (viz., C57BL/6NKorl mice from Korea, C57BL/6NA mice from the United States, and C57BL/6NB mice from Japan) obtained from different sources. The results showed that C57BL/6 N mice derived from various sources exposed to repeated RST resulted in depressive-like phenotypes reflected by a similar degree of behavioral modification and susceptibility to oxidative stress in a duration-dependent manner, except for the distinctive features (increased body weight (BW) and tolerance to the suppression of BW gain by exposure to repeated RST) in C57BL/6NKorl mice. Taken together, the duration-dependent alteration in depressive-like phenotypes by repeated exposure to RST observed in this study may provide valuable insights into the nature of C57BL/6NKorl mice as an alternative animal resource for better understanding of the etiology of depressive disorders and the mechanisms of antidepressant actions.

Influence of three BALB/c substrain backgrounds on the skin tumor induction efficacy to DMBA and TPA cotreatment / 한국실험동물학회지

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.