• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3267-3274
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• 2014

In order to investigate the effects of the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic ${\alpha}$-helical non-cell-selective antimicrobial peptide $L_8K_9W_1$ on the structure, cell selectivity and mechanism of action, we synthesized a series of $L_8K_9W_1$ analogs with double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu in the hydrophobic face of $L_8K_9W_1$. In this study, we have confirmed that the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, or Nleu in the hydrophobic face of $L_8K_9W_1$ let to a great increase in the selectivity toward bacterial cells and a complete destruction of ${\alpha}$-helical structure. Interestingly, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu preferentially interacted with negatively charged phospholipids, but unlike $L_8K_9W_1$ and $L_8K_9W_1$-$\small{D}$-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu involves the intracellular target other than the bacterial membrane. In particular, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu had powerful antimicrobial activity (MIC range, 1 to $4{\mu}M$) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.

• Journal of Life Science
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• v.15 no.4 s.71
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• pp.647-651
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• 2005

The major causative bacteria of food poisoning were Salmonella spp. $(35.6\%)$, Staphylococcus aureus $(11.3\%)$ and Vibrio parahaemolyticus $(3.2\%)$ in our country. In this study we attempted isolation of S. aureus from stools of patients with diarrhea. Sixty-four strains $(9.1\%)$ were isolated from 704 the stools of patients with diarrhea. The enterotoxin was detected from 29 isolates $(45.3\%)$: 24 isolates $(37.5\%)$, 3 isolates $(4.7\%)$ and 2 isolates $(3.1\%)$ were A, B and C type, respectively. In the antibiotic susceptibility, 63 isolates $(98.4\%)$ were resistant to penicillin, 60 isolates $(93.8\%)$ to ampicillin, 35 isolates $(54.7\%)$ to erythromycin, 32 isolates $(50.0\%)$ to gentamycin, 22 isolates $(34.4\%)$ to tetracycline and 20 isolates $(31.3\%)$ to oxacillin. All of S. aureus isolates were susceptible to chloramphenicol and vancomycin, 20 isolates $(31.3\%)$ were methicillin-resistance S. aureus (MRSA). MRSA isolation rate was higher in male $(35.7\%)$ than female $(26.3\%)$. With the exception of two isolates which were resistant only to penicillin, sixty-one isolates were multiple antibiotic resistance.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.207-218
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• 2002

Background : Intensive care units (ICUs) are generally considered epicenters of antibiotic resistance and the principal sources of multi-resistant bacteria outbreaks. The antibiotic resistance in newly opened intensive care unit that has no microbial colonization on and around the devices was investigated. Materials and Methods : The authors analyzed the antibiotic resistance patterns for common hospital acquired-pneumonia pathogens in the ICUs(Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp.) at the newly opened ICU of Hanyang University Medical Center, Kuri Hospital during 6 years(1995-2000). Results : 1) Regarding Staphylococcus aureus, the resistance rate to methicillin was 15% at 1995, 21% at 1996, 20% at 1997, 23% at 1998, 22% at 1999, 55% at 2000. 2) Regarding Pseudomonas aeruginosa, the resistance rate to $3^{rd}$ cephalosporin was 50% at 1995, 50% at 1996, 78% at 1997, 40% at 1998, 77% at 1999, 39% at 2000. Imipenam was 0% at 1995, 27% at 1996, 65% at 1997, 12% at 1998, 16% at 1999, 12% at 2000. Ciprofloxacin was 0% at 1996, 56% at 1997, 36% at 1998, 57% at 1999, 58% at 2000. Tobramycin was 7% at 1995, 10% at 1996, 67% at 1997, 36% at 1998, 65% at 1999, 12% at 2000. Gentamycin was 14% at 1995, 36% at 1996, 67% at 1997, 36% at 1998, 65% at 1999, 12% at 2000. Amikacin was 14% at 1995, 30% at 1996, 61% at 1997, 16% at 1998, 39% at 1999, 18% at 2000. 3) Regarding Acinetobacter spp., the resistance rate to $3^{rd}$ cephalosporin was 92% at 1996, 89% at 1997, 88% at 1998,84% at 1999, 77% at 2000. Imipenem was 50% at 1996, 48% at 1997, 45% at 1998, 49% at 1999, 50% at 2000. Ciprofloxacin was 0% at 1996, 48% at 1997, 33% at 1998, 27% at 1999, 71% at 2000. Tobramycin was 67% at 1995, 100% at 1996, 89% at 1997, 95% at 1998, 87% at 1999, 77% at 2000. Gentamycin was 67% at 1995, 100% at 1996, 89% at 1997, 95% at 1998, 87% at 1999, 83% at 2000. Amikacin was 33% at 1995, 83% at 1996, 82% at 1997, 88% at 1998, 75% at 1999, 69% at 2000. Conclusion : The S.aureus resistance to methicillin, the Pseudomonas aeruginosa resistance to ciprofloxacin, and the Acinetobacter spp. resistance to ciprofloxacin have rapidly increased during 6 years. There is a need to pay speicial attention when using the the antibiotics for the above pathogens. This data may be useful in antibiotic therapy in newly opened intensive care units.

• Pediatric Infection and Vaccine
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• v.9 no.2
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• pp.163-174
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• 2002

Background : To delineate the changes in the causative agents of neonatal sepsis and their antimicrobial susceptibilities in the neonatal intensive care unit and nursery of Hanyang University Hospital during the past 10 years. Methods : Hospital records of 15,144 patients hospitalized at the NICU and nursery of Hanyang University Hospital from 1989 to 1998 were reviewed and neonates diagnosed of neonatal sepsis were sorted and included in the study. The study period was divided into Period A(the first 5 years) and Period B(the second 5 years) to analyse causative agents and their antimicrobial susceptibilities. Results : Neonatal sepsis was diagnosed in 170 patients(1.1%{Period A 1.2%, Period B 1.0%}) among the total of 15,144 inpatients. Two hundred isolates(Period A 109 isolates, Period B 91 isolates) were identified in 186 blood cultures(Period A 99 cultures, Period B 87 cultures) from 170 patients(Period A 91 patients, Period B 79 patients). The average age at the onset of the disease, when the initial blood culture was drawn, was 12.3 days old(Period A 8.8 days, Period B 16.3 days), and the proportion of the early onset disease was 34.7% in Period A and 23.0% in Period B, indicating that neonatal sepsis developed earlier during Period A. Among the isolated organisms including Gram positive bacteria[132(66.0%)], Gram negative bacteria [60(30.0%)], and fungi[8(4.0%)], coagulase negative Staphylococcus(CNS) was the most common organism(69/34.5%), followed by Staphylococcus aureus(36/18.0%), Klebsiella pneumoniae(17/8.5%), Enterococcus(12/6.0%), Enterobacter cloacae(8/4.0%), Escherichia coli(6/3.0%), and Pseudomonas aeruginosae(5/2.5%). The isolated fungi were Candida parapsilosis, Candida albicans, and Trichosporon pullulans. CNS, S. aureus and Acinetobacter baumannii were isolated more frequently in Period A compared to Period B. Antimicrobial susceptibilities of CNS and S. aureus to methicillin and the first generation cephalo sporins were decreased in Period B compare to Period A, those to aminoglycosides were increased in Period B, and vancomycin resistant strains were not identified. K. pneumoniae, Enterococcus, E. coli, and P. aeruginosa were isolated less frequently in Period B, compared to Period A. For K. pneumoniae, antimicrobial susceptibilities to the first generation cephalosporins were low in both Periods A and B, those to tobramycin and gentamicin were increased in Period B, and those to amikacin, ceftriaxone, and trimethoprim-sulfamethoxazole were high in both Periods A and B. Antimicrobial susceptibilities of Enterococcous to ampicillin, penicillin, and the first generation cephalosporins were decreased in Period B, but vancomycin resistant strains were not identified. Conclusion : The occurrence rate of neonatal sepsis during the past 10 years in the NICU and nursery of the Hanyang University hospital was 1.1%, and the most common causitive agents were CNS and S. aureus, to which the antimicrobial susceptibilities to the first line drugs decreased in the later half of the study period with no vancomycin resistant isolates identified. Group B Streptococcus known to be the most common agent causing neonatal sepsis was not identified, and K. pneumoniae was isolated more commonly during the later half of the study period without decreased antimicrobial susceptibilities.

• Journal of Korean Neurosurgical Society
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• v.63 no.1
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• pp.45-55
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• 2020

Objective : Fibrin sealants have been used for hemostasis, sealant for cerebrospinal fluid leakage, and adhesive barrier in neurosurgery. Further, as its clinical use and role of an effective drug delivery vehicle have been proposed. This study was performed to measure antibacterial activity and continuous local antibiotic release from different concentrations of vancomycin-impregnated fibrin sealant in vitro. Methods : Antibacterial activity was investigated by disk diffusion test by measuring the diameter of the growth inhibition zone of bacteria (methicillin-resistant Staphylococcus aureus, ATCC29213) from vancomycin-embedded fibrin sealant disc diluted at five different concentrations (C1-C5; 8.33, 4.167, 0.83, 0.083, and 0.0083 mg/disc, respectively). Continuous and conditioned release of vancomycin concentration (for 2 weeks and for 5 days, respectively) were also measured using high-performance liquid chromatography (HPLC) method. To mimic the physiologic wound conditions with in vitro, conditioned vancomycin release in phosphate buffer solution (PBS) was measured and replaced PBS for five consecutive days, half a day or completely daily. Results : In the disk diffusion test, the mean diameters of bacterial inhibition zone were 2.54±0.07 cm, 2.61±0.12 cm, and 2.13±0.15 cm (C1, C2, and C3 respectively) but 1.67±0.06 cm and 1.23±0.15 cm in C4 and C5, respectively. Continuous elution test elicited the peak release of vancomycin from the fibrin sealant at 48 hours, with continued release until 2 weeks. However, conditioned vancomycin release decreased to half or more on day 2, however, the sustainable release was measured over the therapeutic dose (10-20 ㎍/mL) for 5 days and 4 days in assays of half and total exchange of PBS. Conclusion : This study suggests that fibrin sealant can provide an efficient vehicle for antibiotic drug release in a wide range of neurosurgical procedures and the safe and effective therapeutic dose will be at the concentration embedded of 4.167 mg/disc or more of vancomycin.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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• pp.81-88
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• 2020

Background: Use of appropriate antibiotics for the treatment of pneumonia is integral in patients admitted to intensive care units (ICUs). Although it is recommended that empirical treatment regimens should be based on the local distribution of pathogens in patients with suspected hospital-acquired pneumonia, few studies observe patients admitted to ICUs with nursing home-acquired pneumonia (NHAP). We found factors associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via the emergency room (ER). Methods: We performed a retrospective cohort study of 83 pneumonia patients with confirmed causative bacteria admitted to ICUs via ER March 2015-May 2017. We compared clinical parameters, between patients who received appropriate or inappropriate antibiotics using the Mann-Whitney U, Pearson's chi-square, and Fisher's exact tests. We investigated independent factors associated with inappropriate antibiotic use in patients using multivariate logistic regression. Results: Among 83 patients, 30 patients (36.1%) received inappropriate antibiotics. NHAP patients were more frequently treated with inappropriate antibiotics than with appropriate antibiotics (47.2% vs. 96.7%, p<0.001). Methicillin-resistant Staphylococcus aureus was more frequently isolated from individuals in the inappropriate antibiotics-treated group than in the appropriate antibiotics-treated group (7.5% vs. 70.0%, p<0.001). In multivariate analysis, NHAP was independently associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via ER. Conclusion: NHAP is a risk factor associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via the ER.

• Journal of Dairy Science and Biotechnology
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• v.31 no.2
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• pp.143-152
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• 2013

Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system of animals, has several physiological effects including anti-hypertensive, diuretic, tranquilizing, and anti-stress properties, in humans. The purpose of this study was to investigate Lactobacillus plantarum K74, which was isolated from kimchi and selected as a strain with a high ability to produce GABA, to develop a new starter culture for fermented milk production. L. plantarum K74 produced $134.52{\mu}g/mL$ GABA in MRS broth containing 1% MSG, $212.27{\mu}g/mL$ GABA in MRS broth containing 2% MSG, and $234.63{\mu}g/mL$ GABA in MRS broth containing 3% MSG. The optimum growth temperature of L. plantarum K74 was $34^{\circ}C$, reaching a pH of 4.4 after 18 hours of growth. L. plantarum K74 was most sensitive to novobiocin out of 16 different antibiotics tested, and was most resistant to kanamycin and polymyxin B. L. plantarum K74 did not produce ${\beta}$-glucuronidase, a carcinogenic enzyme, and was comparatively tolerant to bile juice and low pH. Furthermore, it displayed resistance to Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus at rates of 54.9%, 46.3%, and 0.7%, respectively.

• Applied Chemistry for Engineering
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• v.28 no.2
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• pp.198-205
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• 2017

In this study, graviola leaf extracts (GLE) was investigated for the effect of antioxidant, antibacterial, whitening, anti-wrinkle. The antioxidant effect of GLE was measured by an electron donating ability assay. As a result, GLE increased the electron donating ability in a concentration-dependent manner. The antibacterial effect of GLE was found to show the higher antibacterial effect in Methicillin-resistant Staphylococcus aureus CCARM3115 compared with that of ampicillin by a paper disc method. The whitening effect of GLE was also measured by tyrosinase inhibition assay, and it was found that the tyrosinase activity of GLE decreased as the concentration increased. The inhibition activity of tyrosinase involved in hydroxylation reaction which is related to converting L-tyrosine to (DOPA) was higher than that of arbutin's at the concentration ranging from 125 to $250{\mu}g/mL$. In addition, GLE reduced melanin contents of B16-F10 melanoma cells in a dose-dependant manner and decreased to about 76.7% at a concentration of $100{\mu}g/mL$ Regarding wrinkling formation of GLE, an elastase inhibition assay was performed. As a result, GLE and ursolic acid were 10.5% and 56.5%, respectively under the identical concentration. These results suggest that GLE has significant antioxidant and whitening activities, and also may be potentially used as a therapeutic agent for hyperpigmentation treatment as an ingredient of whitening cosmetics.

• Journal of Food Hygiene and Safety
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• v.35 no.4
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• pp.391-397
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• 2020

Human infections with livestock-associated methicillin-resistant/-susceptible Staphylococcus aureus (LA-MRSA/LA-MSSA) have recently been increasing significantly. These LA-MRSA and LA-MSSA strains can be transmitted to individuals who have frequent contact with livestock animals and foods of animal origin. In this study, major virulence potentials of S. aureus such as biofilm formation, antimicrobial peptide resistance, and in vitro hydrogen peroxide (H₂O₂) resistance were assessed using 20 MRSA and MSSA strains isolated from raw milk, beef cattle, and workers in the livestock industry. Static biofilm formation assays revealed that there is no difference in levels of biofilm production between MRSA versus MSSA or bovine- versus human-associated strains. In vitro BMAP (bovine myeloid antimicrobial peptide)-28 susceptibility assays also revealed no difference in the resistance to the antimicrobial peptide between MRSA versus MSSA or bovine- versus human-associated S. aureus strains. However, LA-MRSA strains displayed increased resistance to H₂O₂, which may play an important role in survival and dissemination of the pathogen in livestock. These results provide an important basis for understanding pathogenic potentials of LA-MRSA and LA-MSSA strains in human and animal hosts.

• Journal of Life Science
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• v.27 no.4
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• pp.476-481
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• 2017

Polyphenols are secondary metabolites produced by higher plants and have been used as antiallergic, anticancer, antihypertensive, antiinflammatory, antimicrobial and antioxidant agents. They are generally divided into flavonoids and non-flavonoids. The antimicrobial activity of flavonoids are stronger than that of non-flavonoids. The skeleton structures of flavonoids possessing antimicrobial activity are chalcone, flavan-3-ol (catechin), flavanone, flavone, flavonol and proanthocyanidin. The flavonols are shown antibacterial activity against several gram-positive bacteria (Actinomyces naeslundii, Lactobacillus acidophilus and Staphylococcus aureus) and gram-negative bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella melaninogenica and Prevotella oralis). Among of non-flavonoids, caffeic acids, ferulic acids and gallic acids showed antimicrobial activity against gram-positive (Listeria monocytogenes and S. aureus) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). These are found to be more efficient against the E. coli, L. monocytogenes, P. aeruginosa and S. aureus than antibiotics such as gentamicin and streptomycin. The kaempferol and quercetin showed synergistic effect with ciprofloxacin and rifampicin against S. aureus and methicillin resistant S. aureus (MRSA). Epigallocatechin gallate (EGCG) acts synergistically with various ${\beta}-lactam$ antibiotics against MRSA. In particular, the epicatechin, epigallocatechin (EGC), EGCG and gallocatechin gallate from Korean green tea has antibacterial activity against MRSA clinical isolates and the combination of tea polyphenols and oxacillin was synergistic for all the clinical MRSA isolates.