• Journal of Life Science
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• v.26 no.12
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• pp.1392-1399
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• 2016

Jaspine B is an anhydrophytosphingosine that is isolated from a marine sponge. Because of its structural similarity to sphingosine, it shows anti-cancer effects in human carcinomas. Therefore, this study aims to investigate its anti-proliferative effect on various cancer cells and to correlate its association with the intracellular accumulation of Jaspine B in relevant cancer cells. The anti-proliferative effect of Jaspine B in various cancer cells was determined by a cell viability test, and the intracellular concentration of Jaspine B in relevant cancer cells was determined using mass spectrometry coupled with liquid chromatography. The correlation coefficient and p value between the cytotoxicity and the cell accumulation of Jaspine B were determined using SPSS 16.1. The cytotoxicity of Jaspine B varied depending on the type of cancer cell when compared the $EC_{50}$ values of Jaspine B. Breast and melanoma cancer cells were susceptible to Jaspine B, whereas renal carcinoma cells were resistant. The intracellular concentrations of Jaspine B had a reciprocal correlation with the $EC_{50}$ values in the same cells (r = 0.838). The results suggested that the anti-proliferative effect of Jaspine B was associated with the cellular accumulation of this compound. However, Jaspine B was not a substrate for P-glycoprotein and breast cancer resistance protein, as major efflux pumps caused multidrug resistance. The maintenance of a high intracellular concentration is crucial for the cytotoxic effect of Jaspine B; however, efflux pumps may not be a controlling factor for Jaspine B-related resistance in cancer cells.

• Journal of Life Science
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• v.25 no.7
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• pp.833-838
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• 2015

Multidrug-resistant super bacterial, fungal, viral, and parasitic infections are major health threaten pathogens. However, to overcome the present healthcare situation, among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly produced via various species in nature. AMPs, small host defense proteins, are in charge of the innate immunity for the protection of multicellular organisms such as fish, amphibian, reptile, plants and animals from infection. The number of AMPs identified per year has increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been listed into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11–50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31–70%. This report classified AMP into several categories including biological source, biological functions, peptide properties, covalent bonding pattern, and 3D structure. AMP functions not only antimicrobial activity but facilitates cell biological activity such as chemotatic activity. In addition, fibroblastic reticular cell (FRC) originated from mouse lymph node stroma induced the expression of AMP in inflammatory condition. AMP induced from FRC contained whey acidic protein (WAP) domain. It suggests that the classification of AMP will be done by protein domain.

• Journal of Microbiology and Biotechnology
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• v.16 no.9
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• pp.1377-1383
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• 2006

Among 46 Acinetobacter baumannii isolates collected in 2004, two imipenem-resistant isolates were obtained from clinical specimens taken from patients hospitalized in Busan, Republic of Korea. Two carbapenemase-producing isolates were further investigated to determine the mechanism of resistance. These isolates were analyzed by antibiotic susceptibility testing, microbiological tests of carbapenemase activity, determination of pI, transconjugation test, enterobacterial repetitive consensus (ERIC)-PCR, and DNA sequencing. Two cases of infection by A. baumannii producing the IMP-1 ${\beta}$-lactamase were detected. The isolates were characterized by a modified cloverleaf synergy test and EDTA-disk synergy test. Isoelectric focusing of crude bacterial extracts revealed nitrocefin-positive bands with a pI value of 9.0. PCR amplification and characterization of the amplicons by direct sequencing indicated that the isolates carried a $bla_{IMP-l}$ determinant. The isolates were characterized by a multidrug resistance phenotype, including penicillins, extended-spectrum cephalosporins, carbapenems, and aminoglycosides. These results indicate that the observed imipenem resistance of two Korean A. baumannii isolates was due to the spread of an IMP-1-producing clone. Our microbiological test of carbapenemase activity is simple to screen class B metallo-${\beta}$-lactamase-producing clinical isolates to determine their clinical impact and to prevent further spread. This study shows that the $bla_{IMP-l}$ resistance determinant, which is emerging in Korea, may become an emerging therapeutic problem, since clinicians are advised not to use extended-spectrum cephalosporins, imipenem, and aminoglycosides. This observation emphasizes the importance of having effective control measures in Asian hospitals, such as early detection of colonized patients, isolation procedures, and a judicious use of antibiotics.

• Tuberculosis and Respiratory Diseases
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• v.84 no.4
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• pp.317-325
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• 2021

Background: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are significant public health issues in the world, but the epidemiological data pertaining to HAP/VAP is limited in Korea. The objective of this study was to investigate the characteristics, management, and clinical outcomes of HAP/VAP in Korea. Methods: This study is a multicenter retrospective cohort study. In total, 206,372 adult patients, who were hospitalized at one of the 13 participating tertiary hospitals in Korea, were screened for eligibility during the six-month study period. Among them, we included patients who were diagnosed with HAP/VAP based on the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) definition for HAP/VAP. Results: Using the IDSA/ATS diagnostic criteria, 526 patients were identified as HAP/VAP patients. Among them, 27.9% were diagnosed at the intensive care unit (ICU). The cohort of patients had a median age of 71.0 (range from 62.0 to 79.0) years. Most of the patients had a high risk of aspiration (63.3%). The pathogen involved was identified in 211 patients (40.1%). Furthermore, multidrug resistant (MDR) pathogens were isolated in 138 patients; the most common MDR pathogen was Acinetobacter baumannii. During hospitalization, 107 patients with HAP (28.2%) had to be admitted to the ICU for additional care. The hospital mortality rate was 28.1% in the cohort of this study. Among the 378 patients who survived, 54.2% were discharged and sent back home, while 45.8% were transferred to other hospitals or facilities. Conclusion: This study found that the prevalence of HAP/VAP in adult hospitalized patients in Korea was 2.54/1,000 patients. In tertiary hospitals in Korea, patients with HAP/VAP were elderly and had a risk of aspiration, so they were often referred to step-down centers.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.2
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• pp.155-163
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• 2019

During the time period from 2010 to 2017, out of 162,551 blood specimens, 11,233 (6.9%) specimens were positive for culture and 11,865 strains were cultured. Among the isolates, 47.8% were Gram positive cocci, 38.8% were Gram negative rods, 4.2% were Gram positive bacilli, 6.8% were fungi and 2.3% were anaerobes. When the culture results were compared according to gender, 55.0% (2,732/4,969) of the isolates were found in males and 45.0% (2,237/4,969) were isolated in females. In addition, when categorized according to age group, people in their 70s were the most separated by 28.7% (1,426/4,969) and this showed a great difference from 1.2% (62/4,969) of people in their teens. MRSA decreased significantly from 66.7% in 2016 to 46.8% in 2017. The vancomycin resistance rate of E. faecium was 35.0% (48/137). The ESBL positive rate of E. coli in intestinal bacteria was increased from 17.2% in 2010 to 28.8% in 2017, but the positive rate decreased for K. pneumoniae. 11.8% (14/119) of multidrug-resistant P. aeruginosa (MDRPA) of P. aeruginosa and 64.3% (161/252) of MDRAB of A. baumannii showed high resistance. Because the microbial susceptibility and antimicrobial susceptibility patterns of the blood specimens isolated from all the blood specimens differ according to the time period, region and patients, periodic analyses of different pathogens and understanding the changes in the degree of susceptibility to antimicrobial susceptibility have been conducted in hospitals.

• Journal of Microbiology and Biotechnology
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• v.31 no.5
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• pp.667-675
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• 2021

Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4⁺ T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4⁺ T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4⁺ T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4⁺ T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae. Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.342-348
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• 2020

Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs), which is one of the most common infectious diseases in humans worldwide. Since UPEC is increasingly gaining resistance to many antimicrobial agents, antibiotic therapy of UTI has recently become a great concern. This study examined the epidemiological relationship, and antimicrobial resistance patterns of 84 UPEC isolates obtained from UTI patients in Daejeon, from March to December 2017. Molecular epidemiology was investigated by multilocus sequence typing (MLST), and an antimicrobial susceptibility test was determined using an E-test. In this study, UTI was more common in females (73.8%) than in males (26.2%), and the highest incidence of UTI was observed in the age group in their 70s. Among the 84 UPEC isolates, 59 isolates (70.2%) were multidrug-resistant (MDR), and the major sequence type was ST131 (44 isolates, 52.4%). Interestingly, the rates of MDR in non-ST131 isolates (72.5%) were higher compared to ST131 isolates (68.2%). These results indicate the possibility of the development and spread of MDR in non-ST131 isolates. Effective surveillance networks and continuous research need to be conducted globally to prevent the emergence and international spread of MDR non-ST131 isolates.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.128-136
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• 2002

Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.

• Korean Journal of Environmental Agriculture
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• v.27 no.2
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• pp.156-162
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• 2008

Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, self-limited enteritis to fatal infection in animals and food-borne infection and typhoid fever in humans. Recently, the emergence of multidrug resistant strains of Salmonella spp. causes more serious problems in environment and public health. The present study was investigated the antibacterial effect of Houttuynia cordata ethanol extract(HCEE) for murine salmonellosis. In the cytotoxic effect of HCEE on RAW 264.7 cells, there was no detectable effect with any concentrations between 25 and 100 ${\mu}g/ml$ after 8 h incubation. The bacteriocidal effect of HCEE was not showed on a Salmonella enterica serovar Typhimurium(S. typhimurium). HCEE makes morphological change of the RAW 264.7 cells, and there was significant decreased bacterial uptake and intracellular replication within Salmonella infected cells. And further nitric oxide(NO) production of Salmonella infected RAW 264.7 cells with HCEE was decreased comparing to RAW 264.7 cells without HCEE until 8 h post infection. Oral administration of HCEE showed a therapeutic effect for S. typhimurium infected BALB/c mice. The mortality of HCEE treated mouse was 80% until 12 days, while that of HCEE untreated mouse was 100 % until 8 days after lethal dose of S. typhimurium infection. These data suggested that HCEE has a potency treatment for intracellular replicative pathogen including salmonellosis, brucellosis, tuberculosis, listeriosis etc., and the application of HCEE makes new strategies for safety medicine development without antibiotic resistance bacterial appearance and residue problem in food and solves the public health problem from antibiotic mis- and over use.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.791-797
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• 2009

Purpose : We aimed to investigate the clinical manifestations of and antibiotic resistance in culture-proven childhood salmonellosis. Methods : Clinical manifestations and laboratory data of and antibiotic use in subjects with culture-proven childhood salmonellosis, who were treated at the Chonbuk National University Hospital between September 1998 and August 2008, were analyzed retrospectively. Patients with underlying diseases or concomitant illnesses were excluded. Results : We assessed a total of 72 patients. There were 68 stool culture-positive cases, 7 blood culture-positive cases, and 3 both stool culture- and blood culture-positive cases. Salmonella group D was the most frequent pathogen in stool (63.9%) and blood (71.4%) cultures. Salmonella typhi was isolated in 1 case. Of the 72 patients, 45 (62.5%) were male children, of which 29 (40.3%) were aged <3 years. The patients most commonly presented with diarrhea (90.2%) and fever (83.3%). Leukocytosis (leukocyte count, >$15,000/{\mu}L$) and leukopenia (leukocyte count, <$4,000/{\mu}L$) were detected in 8.3% and 5.6% of the patients, respectively. Elevated serum C-reactive protein concentration (>5 mg/dL) and erythrocyte sedimentation rate (>20 mm/h) were observed in 88.9% and 58.3% of the patients, respectively. Fifty-two (85.2%) of 61 patients who had undergone antibiotic treatment received a third-generation cephalosporin as definitive antibiotic therapy. Multidrug resistance rate was 40.0 % in the first 5 years of the study and 71.4% in the last 5 years. No fatalities occurred in this series. Conclusion : Children with culture-proven salmonellosis showed relatively benign clinical outcomes. Appropriate antibiotic treatment of <2 weeks is probably adequate for those without a suppurative focus of infection. The incidence of antibiotic resistant isolates was recently seen to increase.