반려동물과 관련∙종사자에서 분리된 항생제 내성 대장균의 상관성 분석

학위논문 (박사)-- 서울대학교 대학원 수의과대학 수의학과, 2017. 8. 박용호.Livestocks today are not that much more valuable than they were long ago, we treat our companion animals as if they were far more valuable. In addition, we have seen a huge switch in animal medicine, from a focus on livestocks to a focus on companion animals such as horses, dogs and cats. In the Korean companion animal industry, the market size associated with companion animals is rapidly increasing and estimated to be $5.4 billion by 2020. In addition, more and more Korean people have recognized the importance of horse industry according to the increasing trend of horse-riding. However, limited information is available regarding horse-associated antimicrobial resistant (AR) bacteria in Korea. As first study, we evaluated the frequency and characterize the pattern of AR Escherichia coli (E. coli) from healthy horse-associated samples. Thirty of the E. coli isolates (21%) showed antimicrobial resistance to at least one antimicrobial agent, and four of the AR E. coli (13.3%) were defined as multi-drug resistance. Pulsed-field gel electrophoretic analysis showed the cross-transmissions between horses or horses and environments were detected in two facilities. Although cross-transmission of AR E. coli in horses and their environments was generally low, our study suggests a risk of transmission of AR bacteria between horses and humans. Quinolone (Q) and fluoroquinolone (FQ) are broad-spectrum synthetic antimicrobials used to treat bacterial infections in humans and animals. Since they are very potent antimicrobial agents against Gram-negative bacteria including E. coli, these agents have been widely used to treat a range of infections in companion animals. Consequently, (F)Q resistance has markedly increased worldwide, posing a significant threat to the health of animals and humans. In the second study, we investigated the prevalence and the mechanisms of FQ/Q resistance in E. coli isolates from companion animals, owners, and non-owners. A total of 27 nalidixic acid (NA)-resistant isolates were identified. Of these, 10 isolates showed ciprofloxacin (CIP) resistance. Efflux pump activity was detected in 18 isolates (66.7%), but this was not correlated with the increased minimum inhibitory concentration (MIC). Target gene mutations in Q resistance-determining regions (QRDRs) were the main cause of (F)Q resistance in E. coli. The number of point mutations in QRDRs was strongly correlated with increased MIC (R = 0.878 for NA and 0.954 for CIP). Interestingly, (F)Q resistance mechanisms observed in isolates from companion animals were the same as those in humans. Therefore, a prudent use of (F)Q in veterinary medicine is warranted to prevent the dissemination of (F)Q-resistant bacteria from animals to humans. Companion animals such as horses and dogs are considered as one of the reservoirs of AR bacteria that can be cross-transmitted to humans. The inherent risk of any use of antimicrobials to select for AR bacteria poses a relevant risk for public health by spreading of antimicrobial resistance from animals to humans via direct or indirect contacts. However, limited information is available on the possibility of AR bacteria originating from companion animals being transmitted secondarily from owners to non-owners sharing the same space. To address this issue, in the third place, we investigated clonal relatedness among AR E. coli isolated from dog owners and non-owners in the same college classroom or household. Of 31 E. coli, 20 isolates (64.5%) were resistant to at least one antimicrobial, and 16 isolates (51.6%) were determined as multi-drug resistant E. coli. Pulsed-field gel electrophoretic analysis identified three different E. coli clonal sets among isolates, indicating that cross-transmission of AR E. coli can easily occur between owners and non-owners. The findings emphasize a potential risk of spread of AR bacteria originating from companion animals within human communities, once they are transferred to humans. Antimicrobial resistance is an urgent global problem. There are increasing concerns about the emergence of multi-drug resistant bacteria in humans, animals and environments. The antimicrobial resistance is a complex phenomenon driven by many factors such as the interaction of humans, animals and environmental sources for antimicrobial resistance. Our study also showed that they could be not only reservoirs but also transmitters of antimicrobial-resistant bacteria. Therefore, the aims of combating antimicrobial-resistant bacteria and preserving the efficacy of the currently available antimicrobials in human and veterinary medicine as well as in ecological systems should be addressed in an interdisciplinary effort within a One Health approaches. Addressing this urgent threat requires the multifaceted strategies. Elements include strengthened surveillance of antimicrobial usageimproved antimicrobial stewardship in humans and animalsapproaches to incentivize new antimicrobials developmentincreased research on mechanisms of resistancea prudent use of antimicrobials by veterinarians as well as clinicians.Literature Review 1 I. The genus Escherichia coli 2 II. Use of antimicrobials in animals 5 III-1. Mechanisms of antimicrobial resistance in bacteria 9 III-2. Mechanisms of quinolone resistance 12 1. Mutations in DNA gyrase and topoisomerase IV 13 2. The presence of PMQR genes 15 3. Efflux pump activity 16 IV. The emergence of antimicrobial resistance in animals 18 General Introduction 23 Chapter I. Isolation and characterization of antimicrobial-resistant E. coli from national horse racetracks and private horse-riding courses in Korea 27 I. Introduction 28 II. Materials and methods 29 1. Sampling 30 2. Isolation and identification of E. coli 30 3. Antimicrobial resistance profiling of E. coli isolates 31 4. Detection of antimicrobial resistance and integrase genes 32 5. Determination of O and H serotypes 33 6. Molecular fingerprinting 33 III. Results 34 1. E. coli isolation from the horse-associated samples 34 2. Phenotypic characterization of antimicrobial resistance of E. coli isolates 35 3. Detection of the antimicrobial resistance and integrase genes in AR E. coli isolates 35 4. Serotyping of E. coli isolates 36 5. Genotyping of AR E. coli by PFGE 36 IV. Discussion 37 Chapter II. Mechanisms of quinolone resistance in Escherichia coli isolated from companion animals, owners, and non-owners 50 I. Introduction 51 II. Materials and methods 52 1. Sampling 52 2. Isolation of NA-resistant E. coli from swab samples 53 3. Antimicrobial resistance profiling of NA-resistant E. coli isolates 53 4. Determination of minimum inhibitory concentrations (MICs) of NA and CIP 54 5. Detection of PMQR genes and mutations in QRDRs 55 6. Organic solvent tolerance (OST) assay 55 7. Evaluation of the effect of each (F)Q resistance mechanism on MICs of NA and CIP 56 III. Results 56 1. Isolation of NA or CIP resistant E. coli from companion animals and humans 56 2. Susceptibility of NA-resistant E. coli isolates to other antimicrobials 57 3. Determination of MICs 57 4. Analysis of mutations in QRDRs and detection of PMQR genes 58 5. Measurement of efflux pump activity 59 6. Relative contribution of each (F)Q resistance mechanism to increases in MIC 59 IV. Discussion 60 Chapter III. Probable secondary transmission of antimicrobial-resistant Escherichia coli between people living with and without companion animals 70 I. Introduction 71 II. Materials and methods 72 1. Sampling 72 2. E. coli isolation and identification 73 3. Antimicrobial susceptibility test 73 4. Detection of integrase genes in E. coli isolates 74 5. Molecular fingerprinting 74 III. Results 75 1. Isolation of E. coli from swab samples 75 2. Antibiogram of 31 E. coli isolates 75 3. Detection of integrase genes in E. coli isolates 76 4. Genetic relatedness of E. coli isolates from owners and non-owners 76 IV. Discussion 77 References 85 General Conclusion 118 국문초록 120Docto

Anti-proliferative and apoptotic activities of Müllerian inhibiting substance combined with calcitriol in ovarian cancer cell lines

의과대학/박사Purpose This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. Materials and Methods OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. Results The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time- dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulating the expression of B-cell lymphoma 2 (Bcl-2); and up-regulating the expression of Bcl-2 associated X protein (BAX), caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. Conclusion These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.ope

A therapeutic experience of diffuse cerebellopontine angle meningioma through combined translabyrinthine, infratemporal fossa, and suboccipital craniotomy approach

Meningioma is a slow growing tumor that mainly originates from the intracranial region, but rarely occurs at extracranial region. Once the extracranial meningioma shows diffuse and extensive involvement along the cranial nerves, surgical extirpation of the tumor becomes extremely difficult, and surgical morbidity often follows. We present a single case of en plaque meningioma extended to temporal area and parapharyngeal space, and reviewed the surgical technique for manipulation of facial nerve and postoperative cranial nerve palsy.ope

Fasting and Postprandial Analysis of Bowel Sounds and Plasma 5-hydroxytryptamine Level

Background/Aims: Auscultation of bowel sounds is a traditional technique for evaluating patients with abdominal symptoms. It is, however, subjective and qualitative method in general. Recently, analysis of bowel sounds becomes possible. We analyzed bowel sounds in healthy volunteers and measured platelet depleted plasma 5-hydroxytryptamine (5-HT) that may be associated with postprandial symptoms in irritable bowel syndrome. Methods: We recorded both fasting and postprandial bowel sounds for 30 minutes in 16 healthy volunteers with a sensitive electronic stethoscope attached to a digital recorder. The files were saved in computer as wav files and analyzed with a specialized program. Blood samples were also taken before and 1 hour after meal for 5-HT analysis. Results: Meal challenge made no statistically significant changes in the 5-HT concentrations and all the sound parameters including sound to sound interval, sounds/minute, average of sound amplitudes, sound length, percentage of bowel sounds representing sound clustering and dominant frequency of sounds. Conclusions:Postprandial changes in bowel sounds and plasma 5-HT were insignificant in healthy Korean volunteers.ope

Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta-analysis

Objective: The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis. Methods: The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed. Results: Eleven eligible studies with a total of 4608 patients with OSA were included in this meta-analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08-0.29; p < .01). When studies were stratified by disease severity, the significant differences in hematocrit values between patients and controls were only observed in the severe OSA group (SMD, 0.34; 95% CI, 0.08-0.59; p < .01), but not in the mild and moderate OSA groups. In subgroup analyses according to sex and publication year, significant differences in hematocrit values between patients and controls remained stable in studies with only female patients (SMD, 0.25; 95% CI, 0.12-0.38; p < .01) and in studies published after 2012 (SMD, 0.17; 95% CI, 0.06-0.28, p < .01). Conclusion: Our meta-analysis revealed that the hematocrit value was significantly increased in patients with OSA, particularly in severe patients, compared with that in controls. However, the elevation was modest, and the hematocrit value is expected to be within the normal range in patients with OSA. These data suggest that OSA leads to slight increases in hematocrit but does not cause clinically significant erythrocytosis.ope

Association between Vitamin D Status and Risk of Metabolic Syndrome among Korean Postmenopausal Women

This study aimed to investigate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome along with its associated risk factors in Korean postmenopausal women. This study was performed using data from the KNHANES 2008–2010 study and included 4,364 postmenopausal Korean women. Clinical and other objective characteristics, seasonality, and presence of metabolic syndrome with its five components were evaluated and correlated with the serum levels of 25(OH)D. Although no statistically significant associations were observed between the levels of serum 25(OH)D and the prevalence of metabolic syndrome, the adjusted OR for elevated blood pressure, elevated triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C) showed tendency to decrease sequentially as tertiles of serum 25(OH)D levels increased (p for trends = 0.066, 0.043, and 0.010, respectively). Women in the highest tertile of serum 25(OH)D showed a significant decrease in the prevalence of elevated blood pressure, elevated TGs, and reduced HDL-C as compared with those in the lowest tertile of serum 25(OH)D (p = 0.020, 0.014, and 0.002, respectively). Based on these results, we consider that adequate serum levels of 25(OH)D in Korean postmenopausal women may not entirely indicate a lower risk of developing metabolic syndrome. However, adequate serum levels of 25(OH)D are significantly associated with a decrease in elevated blood pressure, elevated TGs, and reduced HDL-C levels in postmenopausal women.ope

Pyloric Injection of Botulinum Toxin for Treatment of Diabetic Gastroparesis: A Report of Four Cases

Gastroparesis is a disorder of gastric motility that results in delayed gastric emptying. Up to 58% of patients with diabetes mellitus may have diabetic gastroparesis, a syndrome characterized by nausea, vomiting, early satiety, and bloating. The pathophysiology of this disorder is not completely understood, but it is believed to include fundic dysaccommodation, a decrease in gastroduodenal pressure gradient and antral hypomotility. In addition to antral and fundic dysfunction, patients with diabetes may typically have pyloric dysfunction or spasm. Treatment consists of a change in diet to small volume, frequent meals and the use of the prokinetic agents. This case report describes the four patients with severe diabetic gastroparesis whose symptoms persisted despite of dietary changes and the use of prokinetic agents in high doses. All of them were treated with pyloric injection of botulinum toxin and three had significant symptomatic and scintigraphic improvement.ope

Usefulness of Urinary Trypsinogen-2 Dipstick Test for Diagnosis of Acute Pancreatitis

Background/Aims: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis. Methods: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls. Results: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p＝0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992. Conclusions: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.ope

Type of Electric Currents Used for Standard Endoscopic Sphincterotomy Does Not Determine the Type of Complications

Background/Aims: The blended current is usually used for endoscopic sphincterotomy (EST) to minimize bleeding. The pure cutting current may induce less edema of the ampulla and therefore result in less injury to the pancreas theoretically. The aim of this study was to evaluate effects of electric currents used on the development of serum pancreatic enzyme evaluation, clinical pancreatitis or bleeding after EST. Methods: One hundred and eighteen consecutive patients who underwent EST with standard papillotome alone for the treatment of choledocholithiasis were reviewed. All EST had been performed by two endoscopists whose experience on EST was similar: one uses "blended current"(BC group, n=74), while the other uses "pure cutting current" (PC group, n=44). Results: Baseline clinical, laboratory, and procedural parameters were similar in both groups. The incidences of hyperamylasemia and hyperlipasemia were similar between two groups. There was no significant difference in the incidence of clinical pancreatitis between two groups (BC 6.8% vs PC 0.0%, p=0.1557). All episodes of pancreatitis were mild. No episodes of significant bleeding occurred after EST. The incidences of sepsis, cholangitis and perforation were also not different between two groups. Conclusions: Development of complications after standard EST such as hyperamylasemia, clinical pancreatitis, and bleeding may not depend on the electric current used.ope

초고강도 탄소나노튜브 섬유 제조를 위한 이론 및 실험적 연구

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 재료공학부, 2018. 8. 박종래.The purpose of this study is to fabricate ultrahigh-strength carbon nanotube yarns (CNTYs) for which the mechanical properties exced those of conventional high- performance fibers through theoretical and empirical aproaches for manufacturing high-strength CNTYs. Due to the inherently superb mechanical properties and high aspect ratios of CNTs, eforts to produce ultrahigh-strength CNTYs which properties that exced those of conventional high-strength fibers such as carbon fibers have continued over the last few decades. As a result, a variety of CNTY fabrication methods have ben developed since the early 200s up to the present, and it is now posible to produce continuous CNTYs with these methods. Nevertheles, macroscale CNTYs stil fail to exhibit he excelent mechanical performance of nanoscale individual CNTs. To overcome these limitations, various atempts to improve the mechanical strength of CNTYs have recently ben proposed. The mechanical and electrical properties of CNTs difer depending on certain aspects of the nanostructure, such as the length, number of wals, and the diameter of the nanotubes. In aditon, the microstructure of the CNT asembly is closely related to the mechanical and electrical properties of the asembly. Therefore, the most important isue is to control the nanostructure of CNTs and the microstructure of the CNT asembly in order to fabricate ultrahigh-strength CNTYs. Chapter 1 briefly describes the CNTYs and related factors that afect he mechanical properties of yarns. The purpose of this study is to review recent studies on improving these mechanical properties and to uncover isues and solutions that are thus far unresolved. Chapter 2 introduces and presents the atempts made to derive the theoretical corelation betwen the structure and the CNTY strength based on the failure mechanism of CNTYs. First, the relationship betwen the structural parameters of the nanostructures of individual CNTs, the basic constiuents of yarns, and the mechanical strength of the CNTYs is investigated. The efect of the microstructure of the CNT asembly on the strength of CNTYs is then theoreticaly considered. Chapters 3 and 4 discus the influence of the structural factors of CNTs as derived from chapter 2 on the yarn strength. The efect of the nanostructure of the carbon nanotubes on the mechanical properties of CNTYs is investigated by undertaking the synthesis CNTYs made of CNTs with various nanostructures, after which the efects of polymer chains on the internal structures of CNTYs and the yarn deformation behaviors are studied. Finaly, chapter 5 discuses developments related to ultrahigh-strength CNTYs through croslinking considering the nanostructures and microstructures of CNTs based on the theoretical and empirical understanding presented in the previous chapter.Chapter 1 Introduction 1 1.1 Overview of carbon nanotube yarns (CNTYs). 1 1.2 Theoretical consideration of the tensile strength of CNTYs 2 1.3 The state-of-the-art tensile performance of CNTYs. 5 1.3.1 Effect of different yarn formation processes on tensile performance of CNTYs 5 1.3.2 Effect of elementary CNT structure on CNTY strength . 9 1.3.2.1 Length of CNTs . 9 1.3.2.2 Diameter and number of walls of CNTs 11 1.3.2.3 Alignment of CNTs 14 1.3.2.4 Twist angle of CNTs. 17 1.3.3 Routes to improving the tensile strength of CNTYs 21 1.3.3.1 Physical densification 21 1.3.3.2 Polymeric or carbon mediator 26 1.3.3.3 Surface modification of CNTs. 28 1.3.3.4 Crosslinking between CNTs 34 1.4 Aim and scope of this study. 39 1.5 References 41 Chapter 2 Theoretical Approach to High-Specific Strength CNTYs 49 2.0 Major symbols. 49 2.1 Introduction. 50 2.2 CNTY model 51 2.3 Effect of the nanostructure on the CNTY strength 59 2.4 Effect of the bundle size on the CNTY strength. 67 2.5 Conclusion . 68 2.6 References 69 Chapter 3 Empirical Approach 1: Effects of the Nanostructure Characteristics of Individual Component CNTs on the CNTY Strength 72 3.1 Introduction. 72 3.2 Experimental . 74 3.3 Results and discussion. 77 3.4 Conclusion . 88 3.5 References 89 Chapter 4 Empirical Approach 2: Effect of the Bundling Behavior of Individual Component CNTs on the CNTY Strength 93 4.1 Introduction. 93 4.2 Experimental . 96 4.3 Results and discussion. 99 4.4 Conclusion . 125 4.5 References 126 Chapter 5 Empirical Approach 3: Strength Improvement by Controlling the Bundling Behavior and Chemical Crosslinking 132 5.1 Introduction. 132 5.2 Experimental . 135 5.3 Results and discussion. 137 5.4 Conclusion . 157 5.5 References 158 Abstract in Korean 162Docto