Objectives: . A polydioxanone (PDO) stent was developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia-model rabbits. Methods: . In total, 29 New Zealand white rabbits were used: 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. The tracheomalacia model was successfully established in 12 rabbits, and PDO stents were placed in eight of those rabbits. Results: . The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and the mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia-model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0±6.8 and 1.0±0.8 days, respectively. Thus, the PDO stent yielded a significant survival gain (P=0.001). In the tracheomalacia rabbits, stent degradation and granulation tissue were observed 7 weeks after placement, leading to airway collapse and death. Conclusion . We successfully developed a PDO stent and an endoscopic guide placement system. The degradation time of the stent was around 10 weeks in normal rabbits, and its degradation was accelerated in the tracheomalacia model. The mucosal changes associated with PDO stent placement were reversible. Placement of the PDO stent prolonged survival in tracheomalacia-model rabbits.

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.

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.

Objectives: . A polydioxanone (PDO) stent was developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia-model rabbits. Methods: . In total, 29 New Zealand white rabbits were used: 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. The tracheomalacia model was successfully established in 12 rabbits, and PDO stents were placed in eight of those rabbits. Results: . The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and the mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia-model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0±6.8 and 1.0±0.8 days, respectively. Thus, the PDO stent yielded a significant survival gain (P=0.001). In the tracheomalacia rabbits, stent degradation and granulation tissue were observed 7 weeks after placement, leading to airway collapse and death. Conclusion . We successfully developed a PDO stent and an endoscopic guide placement system. The degradation time of the stent was around 10 weeks in normal rabbits, and its degradation was accelerated in the tracheomalacia model. The mucosal changes associated with PDO stent placement were reversible. Placement of the PDO stent prolonged survival in tracheomalacia-model rabbits.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It is characterized by the accumulation of lipids without alcohol intake and often progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver diseases such as cirrhosis or cancer. Although animal models have greatly contributed to the understanding of NAFLD, studies on the disease progression in humans are still limited. In this study, we used the recently reported high-fat L-methionine-defined and choline-deficient (HFMCD) diet to rapidly induce NASH and compared the responses to HFMCD in ICR mice from three different countries: Korea (supplied by the National Institute of Food and Drug Safety Evaluation), USA, and Japan during 6 weeks. Feeding HFMCD did not cause significant differences in weight gain in comparison with mice fed control diet. Relative weight of the liver increased gradually, while the relative weight of the kidneys remained unchanged. The parameters of liver injury (serum activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) increased rapidly from 1 week and remained elevated for as long as 6 weeks. Histopathological analysis showed that the accumulation of hepatic lipids induced by HFMCD was prominent at 1 week after diet supplementation and increased further at 6 weeks. Inflammatory markers were significantly increased in a time-dependent manner by HFMCD. The mRNA levels of TNF-α and IL-6 were elevated approximately 15-fold relative to control diet and that of IL-1β was increased more than 20-folds at 6 week after the onset of HFMCD intake. In addition, mRNA expression of fibrosis markers such as α-SMA, TGFβ1, and Col1a1 were also significantly increased at 6 week. In summary, the responses of Korl:ICR mice by intake of HFMCD diet were similar to those of ICR mice from other sources, which suggests that Korl:ICR mice is also a useful resource to study the pathogenesis of diet-induced NAFLD.

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.
Acetaminophen ; Alanine Transaminase ; Animals ; Cell Death ; Cytochrome P-450 CYP2E1 ; Cytochromes ; Glutathione ; Humans ; Injections, Intraperitoneal ; Korea ; Lipid Peroxidation ; Liver ; Male ; Malondialdehyde ; Mice ; Mice, Inbred ICR ; Necrosis ; Oxidative Stress ; Rats

Rifampin is one of the first line drugs for treating tuberculosis, but it might be associated with serious adverse effects, including renal failure. We report here on a case of a 57-year-old patient who developed Henoch-Shonlein purpura during antituberculosis therapy that included rifampin. The patient converted to negative on the AFB smear for tuberculosis two weeks after the initial administration of antituberculosis medication. After treatment for 60 days, this patient was diagnosed with Henoch-Shonlein purpura by the purpura lesion on the lower legs, the leukocytoclastic vasculitis, the renal impairment and the pathological examination. After stopping rifampin, the skin lesions disappeared in about 10 days and his renal function gradually improved. This case study showed that Henoch-Schonlein purpura can be caused by rifampin during antituberculosis therapy and we recommend that the use of rifampin should be restrained when clinical symptoms of Henoch-Shonlein purpura are observed.
Acute Kidney Injury ; Humans ; Leg ; Middle Aged ; Purpura ; Purpura, Schoenlein-Henoch ; Renal Insufficiency ; Rifampin ; Skin ; Tuberculosis ; Vasculitis ; Vasculitis, Leukocytoclastic, Cutaneous

PURPOSE: Recent studies indicate that Fas and Fas Ligand (Fas-L) are implicated in autoimmune endocrine diseases and tumors of the thyroid. In this study we tried to elucidate the expression stati of Fas and Fas-L in some kinds of thyroid neoplasms, and their relationships with 4 prognostic factors in papillary thyroid cancer (i.e., size, lymph node metastasis, capsule invasion, age). METHODS: 66 cases of thyroid neoplasm including 45 cases of papillary cancer (PTC), 3 of a follicular cancer (FTC), 1 of a poorly differentiated cancer (PDC), 1 of a undifferentiated cancer (UC), 7 of follicular adenoma (FA), and 9 of nodular hyperplasia (NH) were examined, and estimated as negative, weak positive and strong positive about the Fas and Fas-L expression by the immunohistochemical staining intensities. We then collected and compared the differrences between benign and malignant tumors. The expressions of Fas and Fas-L in papillary thyroid cancers were evaluated relating to the differences in the prognostic factors (i.e., the size, lymph node status, capsule invasion, and age of the patients). RESULTS: Malignant thyroid tumors revealed stronger staining intensity than benign neoplasms. In papillary thyroid cancers, Fas-L staining intensities were significantly stronger in the cases with perithyroidal lymph node metastasis, or in those of 45 years old or over than in those with no lymph node metastasis, or younger than 45 years. CONCLUSION: Both Fas and Fas-L are implicated in thyroid tumorigenesis and revealed stronger staining intensities in malignant than benign tumors, and the Fas-L staining intensities may have some prognostic implications at least in papillary thyroid cancers.
Adenoma ; Carcinogenesis ; Endocrine System Diseases ; Fas Ligand Protein* ; Humans ; Hyperplasia ; Lymph Nodes ; Middle Aged ; Neoplasm Metastasis ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: In recent years, knowledge of bacterial resistance to antimicobials has expanded in important ways. Availability of an increasing number of antibiotics allows more precise individualization of resistance phenotypes and recording susceptibility results as patterns or phenotypes is valuable for both surveillance and patient care. If the patterns of resistance to panels of related antimicrobials are considered the underlying mechanisms can often be inferred. And the inferred mechanisms make the clinician to be advised to use alternative treatment. Interpretation of resistance phenotypes is based on the comparison of clinical isolates with prototype susceptible bacteria belonging to the same species. But interpretative reading of antimicrobial susceptibility tests requires an immense knowledge of antibiotics. Such interpretative reading is best achieved by computerized expert systems. METHODS: The authors attempt to determine phenotypes for the clinically isolated strains for each class of drugs tested by the Vitek 2 systemTM(bioMerieux, Marcy I'Etoile, France) using the Advanced Expert SystemTM(AES, bioMerieux, Marcy I'Etoile, France). A total of 91, 107, 89, 65, 251, 113, 47, 33, 23, 122 and 110 isolates of Staphylococcus aureus, coagulase negative staphylococci, Enterococcus faecalis, Enterococcus facium, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Enterobacter aerogenes, Pseudomonas aeruginosae and Acinetobacter baumannii, were examined respectively. RESULTS: Biological correction based on the phenotype was recommended from 2.2% of E. faecalis to 46.8% of S. marcescens and therapeutic correction, from 7.3% of A. baumannii to 60.9% of E. aerogenes. A total of 25, 26, 18, 19, 22, 22, 15, 15, 17, 19, 19 phenotypes of S. aureus, coagulase negative staphylococci, E. faecalis, E. facium, E. coli, K. pneumoniae, S. marcescens, E. cloacae, E. aerogenes, P. aeruginosa and A. baumannii, were detected respectively. Association of resistance mechanism from S. aureus, coagulase negative staphylococci, E. coli, K. pneumoniae, S. marcescens, show 10, 11, 6, 4 and 3 pairs from resistant phenotypes, respectively. CONCLUSION: Vitek AES potentially provides a tool to assist the development of antimicrobial susceptibility interpretation in the clinical microbiology laboratory. The inferred mechanisms make the clinician to be advised to use alternative treatment.
Acinetobacter baumannii ; Anti-Bacterial Agents ; Bacteria ; Cloaca ; Coagulase ; Enterobacter aerogenes ; Enterobacter cloacae ; Enterococcus ; Enterococcus faecalis ; Escherichia coli ; Expert Systems ; Klebsiella pneumoniae ; Patient Care ; Phenotype* ; Pneumonia ; Pseudomonas aeruginosa ; Serratia marcescens ; Staphylococcus aureus

Although most persons infected with Helicobacter pylori harbor a single strain of the organism, multiple strain colonization in the same patient is also occasionally reported in developed countries. The aims of this study were to determine the prevalence of multiple strain colonization in Korean patients and to detect the cagA, iceA1, and babA status of H. pylori isolated from the antrum and body of the stomach. H. pylori was obtained from 35 patients from the antrum and body of the stomach. The genomic diversity of H. pylori was determined by random amplified polymorphic DNA analysis. The status of cagA, iceA1, and babA genes of H. pylori was assessed by polymerase chain reaction with appropriate primers. Clearly different diversity patterns were identified among the isolates from 35 individual patients. Eighteen (51.4%) patients had a single strain of H. pylori. Eight (22.9%) and nine (25.7%) patients had subtypically (one or two bands difference) and typically (clearly different pattern) different strains of H. pylori in the antrum and body, respectively. Among the 70 isolates of H. pylori from 35 patients, the positive rates of 349-bp and 208-bp cagA gene fragments and the iceA1 gene were 68/70 (97.1%), 68/70 (97.1%), and 58/70 (82.9%), respectively. However, the babA gene was found in 22/66 cases (31.4%). In five out of 18 patients with a single strain, the genetic status of cagA, iceA1, and babA varied between the isolates from the antrum and the body. In 8/17 patients with subtypically or typically different strains, the gene status differed between antrum and body isolates. The prevalence of co-colonization with typically or subtypically different strains is high in Korea, and sub-clones with different pathogenic gene status exist within strains of identical RAPD patterns.
Colon ; Developed Countries ; DNA ; Helicobacter pylori* ; Helicobacter* ; Humans ; Korea ; Polymerase Chain Reaction ; Prevalence ; Pyloric Antrum* ; Stomach