• The Korea Journal of Herbology
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• v.35 no.3
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• pp.47-54
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• 2020

Objective : Infectious diseases are a growing problem worldwide by Methicillin-resistant Staphylococcus aureus (MRSA). Daehwangmokdan-tang is one of the oriental medicine prescriptions contained in Principles and Practice of Eastern Medicine. This study investigated the antibacterial activity of EtOH 70% extracts of Daehwangmokdan-tang (DMT) which prescription is composed of oriental medicine against MRSA. Methods : The antimicrobial activity and active concentration of MRSA were verified by measuring the minimum inhibitory concentration (MIC) of DMT. In addition, the effects of the disease were checked by treating the existing antibiotics and large ethanol extract in parallel, and the extent of growth suppression was checked over time. In addition, cell membrane permeability experiment confirmed the effect of large DMT on the immunity mechanism of MRSA. Results : TThe minimum inhibitory concentration of DMT against MRSA is 500 ~ 2000 ㎍/㎖ by broth dilution method. In the checkerboard method, the combinations of DMT with antibiotics has partial synergistic effect or synergy effect and DMT markedly reduced the MICs of the antibiotics oxacillin (OX), gentamicin (GEN) against MRSA. In the inhibition of resistance mechanism of DMT against MRSA, the expression of resistance gene and protein about β-lactam antibiotic was reduced. Also, we observed the effect of DMT about cell membrane permeability against MRSA, and confirmed that DMT suppressed growth of strains by increasing cell membrane permeability and energy metabolism. Conclusion : Basis on the result, we speculate that DMT may be useful for the treatment of MRSA infections when used in combination with β-lactam antibiotic.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.12
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• pp.1784-1789
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• 2006

Two experiments were conducted to determine the effect of phytobiotics and organic acids on growth performance of nursery pigs as an alternative to antibiotics. Phytobiotics refer bioactive compounds from plant materials including essential oils and herbal extracts. In Exp. 1,144 pigs, weaned at 23.4${\pm}$0.3 d age, were allotted to three dietary treatments. Treatment diets were: 1) NC (no antibiotics and no phytobiotics); 2) PC (NC+carbadox, 50 mg/kg); and 3) PB (NC+phytobiotics; 0.1% PEP1000-$1^{(R)}$. Each treatment had six replicates with eight pigs per pen. Pigs were fed the experimental diets for 5 wks in 3 phases (phase 1 for 2 wk; phase 2 for 2 wk; phase 3 for 1 wk). In Exp. 2, 192 pigs, weaned at 19.2${\pm}$0.3 d age, were allotted to three dietary treatments: 1) NC; 2) PC; and 3) PBO (NC+phytobiotics; 0.2% or 0.1% PEP1000-$1^{(R)}$ and organic acids; 0.4% or 0.2% $Biotronic^{(R)}$for the phase 1 and 2, respectively) with eight replicates per treatment and eight pigs per pen. Pigs were fed the assigned diets for 5 wks in 2 phases (phase 1 for 2 wk; phase 2 for 3 wk). Body weights were measured at the beginning of the experiment and at the end of each week in both Exp. 1 and 2. Feed intake was measured at the end of each week in both Exp. 1 and 2. Diarrhea score was measured daily during the entire period for Exp. 1 and during the phase 1 for Exp. 2. In Exp. 1, the PC had a higher (p<0.05) overall ADG than the NC, but the overall ADG of the PB did not differ (p>0.05) from the NC or the PC. In Exp. 2, the overall ADG did not differ (p>0.05) among all the treatments during the entire experimental period. The overall ADFI and the overall gain:feed ratio did not differ (p>0.05) among all the treatments during the entire experimental period in both Exp. 1 and 2. The PC had a higher (p<0.05) overall diarrhea score (harder stools) than the NC and the PB in Exp. 1, and a higher (p<0.05) overall diarrhea score than the NC in Exp. 2. The overall diarrhea score of the PB and the PBO did not differ (p>0.05) from the NC or the PC in Exp. 1 and 2. Results from this study show that the growth of pigs fed the diets with phytobiotics or the combination of phytobiotics and organic acids did not differ from those both with antibiotics and without antibiotics when tested in an environmentally controlled research facility. Further experiments are required to study the growth performance in disease challenged conditions.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.1-13
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• 2015

Objectives Methicillin-Resistant Staphylococcus aureus (MRSA) is a human pathogen and a major cause of hospital-acquired infections. New antibacterial agents that have not been compromised by bacterial resistance are needed to treat MRSA-related infections. In this study, we investigated the antimicrobial activity ofethanol extract of Haedokgeumhwa-san (HGH) which prescription is composed of korean medicine against MRSA. Methods The antibacterial activity of HGH extract was evaluated against MRSA strains by using the Disc diffusion method, broth microdilution method (minimal inhibitory concentration; MIC), checkerboard dilution test, and time-kill test; its mechanism of action was investigated by bacteriolysis, detergent or ATPase inhibitors. The checkerboard dilution test was used to examined synergistic effect of ampicillin, oxacillin, ciprofloxacin, vancomycin, gentamicin and norfloxacin in combination with HGH ethanol extract. A time-kill assay was performed a survival curve which was obtained by plotting viable colony counts depending on time on bacterial growth. Results The minimum inhibitory concentration (MIC) of ethanol extract (HGH) ranged from 1,000 to $2,000{\mu}g/mL$ against all the tested bacterial strains, respectively. We are able to confirm that HGH extract has potentially strong antibacterial activity. In the checkerboard dilution test, fractional inhibitory concentration index of HGH in combination with antibiotics indicated synergy or partial synergism against S. aureus. A time-kill study showed that the growth of the tested bacteria was considerably inhibited after 8 hr of treatment with the combination of HGH with selected antibiotics. For measurement of cell membrane permeability, HGH $250{\sim}1,000{\mu}g/mL$ along with concentration of Triton X-100 (TX) and Tris-(hydroxymethyl) aminomethane (Tris) were used. In the other hand, N,N-dicyclohexylcarbodimide (DCCD) and Sodium azide ($NaN_3$) was used as an inhibitor of ATPase. TX, Tris, DCCD and $NaN_3$ cooperation against S. aureus showed synergistic action. Accordingly, antimicrobial activity of HGH was affected by cell membrane and inhibitor of ATPase. Conclusions These results suggest that Haedokgeumhwa-san extract has antibacterial activity, and that HGH extract offers a potential as a natural antibiotic against MRSA.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.55-61
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• 2015

Objectives : Yongdamgosam-hwan(YGH) has been used as a traditional medicine from old times for antiinflammatory effects. Streptococcus mutans(S. mutans) is known as a prime bacteria responsible for causing caries by forming a biofilm referred to as dental plaque on the tooth surface. But antimicrobial activity of YGH with dental disease is not sufficiently understood. This study was designed to investigate the effects of YGH ethanol extract on antimicrobial effect against Streptococcus mutans.Methods : The antimicrobial effect of YGH ethanol extract was assessed by the paper disk diffusion method and optical density method to determine minimum inhibition concentration(MIC), also observed by fractional inhibitory concentration index(FICI) and time-kill assay to figure out the synergic effect on the combination of YGH ethanol extract with antibiotics.Results : The YGH ethanol extract 500 μg was 7.5-8.5 mm diameter of clear zone of inhibition against Streptococcus mutans in a concentration-dependent manner and MIC was 250 μg/mL. The administration of the ethanol extract in combination with gentamicin and streptomycin induced a reduction of ≥4-8-fold in all tested bacteria. Furthermore, time-kill study was found that a combination of YGH ethanol extract with oxacillin and streptomycin produced a more rapid decrease in the concentration of bacteria CFU/mL than the YGH ethanol extract or antibiotics alone.Conclusions : As a result, the YGH ethanol extract has good antimicrobial effects. And the results suggest that YGH could be employed as a natural antibacterial agent in dental care products.

• Restorative Dentistry and Endodontics
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• v.43 no.3
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• pp.28.1-28.16
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• 2018

This study investigated the latest findings and notions regarding 'triple antibiotic paste' (TAP) and its applications in dentistry, particularly endodontics. TAP is a combination of 3 antibiotics, ciprofloxacin, metronidazole, and minocycline. Despite the problems and pitfalls research pertaining to this paste has unveiled, it has been vastly used in endodontic treatments. The paste's applications vary, from vital pulp therapy to the recently introduced regeneration and revascularisation protocol. Studies have shown that the paste can eliminate the root canal microorganisms and prepare an appropriate matrix for further treatments. This combination is able to remove diverse groups of obligate and facultative gram-positive and gram-negative bacteria, providing an environment for healing. In regeneration protocol cases, this allows the development, disinfection, and possible sterilization of the root canal system, so that new tissue can infiltrate and grow into the radicular area. Moreover, TAP is capable of creating a discipline in which other wanted and needed treatments can be successfully performed. In conclusion, TAP, as an antibacterial intracanal medication, has diverse uses. Nevertheless, despite its positive effects, the paste has shown drawbacks. Further research concerning the combined paste and other intracanal medications to control microbiota is a must.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.44-53
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• 1999

The resistant strains due to the extended-spectrum $\beta$-lactamase (ESBL) were susceptible to cefatrizine combined with clavulanic acid. The purpose of this study was to evaluate the in vitro and in vivo antibacterial activities of cefatrizine/clavulanic acid (CTRZ/CV) combination at a ratio of 2 : 1 in comparison with cefaclor (CCLO), cefuroxime (CRXM), cefuroxime axetil (CRXMA) and amoxicillin/clavulanic acid (AMXCCV). CTRZ/CV showed good activity against laboratory strains of gram-positive and gram-negative bacteria and exhibited excellent antibacterial activity against $\beta$-lactamase-producing strains. The bactericidal activity of CTRZ/CV was superior to that of CCLO and CRXM, and almost equal to that of AMXCCV against the $\beta$-lactamase-producing strains. The in vitro results were substantiated. by in vivo mouse experimental infection studies with $\beta$-lactamase-producing and non-producing strains. In mixed experimental infection due to $\beta$-lactamase-producing and non-producing strains, the therapeutic efficacy of CTRZ/CV was superior to that of CTRZ, CCLO, CRXMA and AMXCCV. In respiratory tract infection in mice due to Klebsiella pneumoniae EB4O, CTRZ/CV was more erective than CCLO, CRXMA and AMXCCV and also more efficacious than CCLO, CRXMA and AMXCCV in urinary tract infection in mice due to Escherichia coli EB13. These results indicate that CTRZ/CV is a useful drug for the treatment of infection caused by $\beta$-1actamase-producing strains including ESBL-producing strains.

• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.828-837
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• 2024

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.

• Applied Biological Chemistry
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• v.40 no.1
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• pp.23-29
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• 1997

To develop novel cephem antibiotics, We have synthesized a new compound, named YH-487, by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-ACA, respectively. Several characteristics such as structure, antibiotic spectrum, action mechanism, stability against ${\beta}-lactamase$ and synergistic effect were investigated. Anti-bactericidal activity of YH-487 against gram-positive and gram-negative bacteria were superior to that of the other cephem antibiotics. We have examined the action mechanisms of YH-487 using penicillin binding protein (PBP) assay, and found that the bactericidal activity was obtained by inhibiting PBP-1A, PBP-1B and PBP-3. YH-487 showed synergistic effect with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa. In addition, YH-487 was effective against Enterobacter cloacae in combination with amikacin. Based on the above observations, YH-487 was classified as a novel third-generation ${\beta}-lactam$ antibiotics.

• Journal of the korean academy of Pediatric Dentistry
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• v.39 no.1
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• pp.43-50
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• 2012

The concept of revascularization of necrotic pulps regained interest and became an alternative conservative treatment option for young permanent teeth with immature roots. Revascularization of immature teeth with apical periodontitis depends mainly on disinfection of the canal. Since the infection of the root canal system is considered to be polymicrobial, a combination of drugs would be needed to treat the diverse flora. A triple antibiotic mixture of metronidazole, ciprofloxacin, and minocycline was used as an intracanal medicament. However, discoloration was developed after applying the triple antibiotic mixture. It is believed that the marked discoloration is related to the use of minocycline. The aim of this article was to present cases of coronal discoloration after triple antibiotic therapy in immature tooth and was treated with bleaching technique to control coronal discoloration. In conclusion, revascularization by using triple antibiotics promotes a paradigm shift in treating endodontically involved permanent teeth. However, we should understand that triple antibiotics containing minocycline induces tooth discoloration. Further research to prevent coronal discoloration should be investigated and suggested for the safe use of triple antibiotics.

• Journal of fish pathology
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• v.13 no.2
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• pp.111-119
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• 2000

One hundred and twenty three strains of bacterial flora collected from Kunsan bay and examined for drug resistance to 9 antibiotics. The isolated and examined bacteria were Vibrio spp.(44 strains), Pseudomonas spp.(42 strains), Aeromonas spp.(26 strains), Moraxella spp.(9 strains), Enterobacteria spp.(6 strains), Bordetella spp.(3 strains), Alkaligenesis spp.(3 strains), Staphylococcus spp.(3 strains), and Flavobacterium spp.(2 strains). The drugs used were Ampicillin(AM), Penicillin-G(PM), Rifampicin(RF), Streptomycin(SM), Oxolinic acid (OA), Nalidixic acid(NA), Oxytetracycline(OT), Amikacin(AK), and Enorfloxacin(EF). Forty two strains were found to be sensitive to all drugs. The remaining strains showed resistance to various combinations of drugs. Among the resistant strains were mostly restricted to AM(54 strains/43.9%), PM(47 strains/38.2%), RF(35 strains/28.4%), SM(9 strains), OA(5 strains/ 4.06%), and NA(1 strains/0.8%), in combination at high degree showing 15 different drug resistant patterns. The most frequently showed resistant patterns were AM-PM-RF(16 strains/13.4%), AM-PM(8 strains/6.5%), and PM-RF(7 strains/5.6%). These results suggested that Kunsan bay were contaminated with various strains of highly resistant strains to drugs(AM, PM and RF). These results suggest that high levels of various antibiotics have already been introduced to Kunsan bay. Furthermore it seems that chemotherapy of fish disease has become extremely difficult because of the acquirement of multi-drug resistance to wide range of antibiotics.