• Journal of Environmental Science International
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• v.17 no.2
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• pp.249-255
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• 2008

The experiment was conducted to determine effect of the mixed herbal medicine for the substitution of antibiotics on the performance of laying hens. Day old hyline 1,500 layer chicks were randomly assigned to 4 treatments. Control were 600 chicks and there were three treatments of each 300 chicks. The 4 treatments were as follows: the mixed herbal medicine 0.1%(T-1), 0.3%(T-2) and 0.5%(T-3) after removed antibiotics on commercial feed and commercial feed( control) from 5th week to 13th week, each treatment was replicated 3 times and from 14th week to 18th week. Each 100 hens of the mixed herbal medicine 0.1%(CT-1), 0.3%(CT-2) and 0.5%(CT-3) were moved to cage. Body weight were measured on 4th, 8th, 13th week and feed intake, mortality were measured on every weeks. Body weight at fourth week, all treatments tended to be higher than control and T-3 statistically was highest(p<0.01). On 8th week, also treatments statistically high and T-1 was highest(p<0.01). But 12th week, there was not significantly different among treatments. Therefore it will be possible that the mixed herbal medicine substitute for antibiotics after vaccination. Mortality was not different between treatment and control overall rearing period. Early laying period($19{\sim}41wk$), T-2 showed highest feed intake(107.1g) among treatments, later laying period($42{\sim}77wk$), T-1 showed highest feed intake(134.3g) and was not any different among each treatments.

• Journal of Environmental Science International
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• v.17 no.5
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• pp.537-546
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• 2008

The experiment was conducted to determine the effect of the mixed herbal medicine for the substitution of antibiotics on the performance of laying hens. Day old hyline 1,500 layer chicks were randomly assigned to 4 treatments. Control were 600 and three each treatment was 300. Eggs were collected at every weeks for measuring egg production and week 26, 27, 28 for chemical analyses. Chemical analyses were done for fatty acid profile of egg yolks, amino acid, antibiotics residue in eggs(collect eggs after supplying OTC 21ppm/bird/day to control for four day at 26, 27, 28) during the laying period($19{\sim}77wk$). On $0{\sim}4$ week, T-3 showed higher feed intake than those fed the other diets and on $5{\sim}13$ week, T-2 showed highest feed intake among treatments. After birds were moved ($14{\sim}18$ wk) CT-3 showed highest, but for overall rearing period, there was not significantly different among treatments. In conclusion the mixed herbal medicine did not tended to influence palatability to rearing birds. Egg quality(egg yolk color, haugh unit, eggshell breaking strength) showed no difference among treatments. Ratio of unsaturated fatty acid (mg/100g)/saturated fatty acid (mg/100g) was not difference among treatments, but linolenic acid and docosahexaenoic acid(DHA) of the mixed herbal medicine treatments showed higher then control. The antibiotics residue of CT, T treatments egg was not detected and control was not detected or below allowance. In conclusion the mixed herbal medicine can be possible to feed laying hen without antibiotics.

• KDI Journal of Economic Policy
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• v.30 no.2
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• pp.129-155
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• 2008

The rate of antibiotics prescription for an acute airway infection significantly varies depending upon the diagnosis type, specialty, and the location of the hospital along with many other related factors. The objective of this study is to empirically investigate the possible relationship between the antibiotics prescription rates for an acute airway infection and the degree of competition in the hospital market regions of mainly the providers of primary medical care services such as clinics, internal medicines, pediatrics and otorhinolaryngology department. Using the data from Health Insurance Review and Assessment Service (HIRA) regarding the hospitals' antibiotics prescription rates for the acute airway infection and controlling for selected variables of demand and supply sectors, this study tries to figure out that the degree of competition in the hospital market, regardless of what type of competition indexes we employed, has a statistically significant effect on the variations of antibiotics prescription rate of the clinics in local areas. This result implies that as an economic consideration itself, the change in the degree of competition in the hospital market can play a crucial role influencing the treatment behaviors of the medical doctors. More specifically, this study reveals that as the degree of competition increases the antibiotics prescription rate goes up. This result means that if the market becomes more competitive in a specific region so that it might cause a reduction in doctor's income, doctors with rational decision-making process, recognize that the benefit created from inducing patients' seemingly unnecessary demand for medical care (income effect) would be higher than the costs associated with sustaining their targeted income (substitution effect). It is because that the doctors are more likely to prescribe antibiotics which create relatively higher margins than other medical care services in order to sustain their targeted income when the hospital market competition becomes tighter. Even though this study empirically confirms that antibiotics prescription can be affected by the economic incentives, it still raises following issues as limitations of the study: first issue is about the representativeness of the hospital regions segregated for this study, which might be weak in explaining whether these regions are mutually exclusive in reality. Patients actually consider the quality of services, transportation cost, time costs, and any other related factors choosing the doctors or hospitals, and in that sense, this study rules out 'border-crossing' in using the medical care services. Second issue arises in capturing the data of antibiotics prescription rate. Since we use the average rate for each medical institution, we cannot figure out the average rate for each patient so that we are not able to control for the variation of patients' medical conditions. It is because of the unavailability of data regarding each patient's medical condition from HIRA. Thirdly, since this study mainly analyzes the medical institutions providing primary care such as clinics, internal medicines, pediatrics, and otorhinolaryngology department, it is skeptical of whether those institutions can represent the hospital market in respective regions and truly reflect the degree of competition. It needs to extend the study areas and disease types as well as any micro data for future studies.

• Journal of Animal Environmental Science
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• v.17 no.1
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• pp.1-10
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• 2011

This study was conducted to investigate the actual situation of animal medicine use in Hanwoo farms, which were a total of 114 farms. Items surveyed were preference of animal medicine, choice criterion, purchase route, purchase frequency, antibiotics substitution products, etc. Data were collected from May to June, 2010. The kinds of animal medicine which preferred in Hanwoo farms is probiotics (40.4%). Whereas the lowest preference is immunizing agent (12.3%). There was significant difference among regional group (p<0.05), and the significant difference was also found in different farm size group (p<0.05). The factor of choice for purchase of animal medicine was efficiency (31.6%), first of all. There was significant difference among regional group (p<0.05). The purchase route of animal medicine was mostly supplied with the help of government (41.6%). The significant difference were showed in regional group (p<0.05). But that was not found in farm size group (p>0.05). The highest frequency at purchasing antibiotics was less than 1 time per 1 year (38.6%). There was statistically significant difference among regional group (p<0.05). However, there was not significant difference among farm size group (p>0.05). Probiotics of antibiotics substitution products was mostly preferred (50.9%).

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2809-2812
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• 2014

The 43-residue defensin-like peptide coprisin, which is isolated from dung bettle, Copris tripartitus, is a potent antimicrobial peptide. In our previous work, we determined the tertiary structure of coprisin and found that alpha helical region of coprisin from residue 19 to residue 30 is important for its antimicrobial activities. Here, we designed cop12mer and cop9mer analogs of coprisin based on the tertiary structure of coprisin. To investigate the relationship between hydrophobicity and antimicrobial activities and develop the potent peptide antibiotics, we designed cop9mer-1 with substitution of $His^2$ with Trp in cop9mer. The results showed that cop9mer-1 has higher toxicities as well as improved antimicrobial activities compared to cop9mer. In order to reduce the toxicity of cop9mer-1, we designed cop9mer-2 and cop9mer-3 with substitution of $Cys^3$ with Lys or Ser. Substitution of $Cys^3$ with these hydrophilic amino acids results in lower cytotoxicities compared to cop9mer-1. Cop9mer-2 with substitution of $Cys^3$ with Lys in Cop9mer-1 showed high antibacterial activities against drug resistant bacteria without cytotoxicity. Antibiotic action of cop9mer-1 analog appears to involve permeabilization of the bacterial cell membrane while cop9mer-2 and cop9mer-3 may have different mechanism of action. These results imply that that optimum balance in hydrophobicity and hydrophilicity in these 9-meric peptides plays key roles in their antimicrobial activities as well as cytotoxicities.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.1030-1036
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• 2018

Bacillus strains produce various types of antibiotics, and random mutagenesis has traditionally been used to overproduce these natural metabolites. However, this method leads to the accumulation of unwanted mutations in the genome. Here, we rationally designed a single nucleotide substitution in the degU gene to generate a B. subtilis strain displaying increased plipastatin production in a foreign DNA-free manner. The mutant strain (BS1028u) showed improved antifungal activity against Pythium ultimum. Notably, pps operon deletion in BS1028u resulted in complete loss of antifungal activity, suggesting that the antifungal activity strongly depends on the expression of the pps operon. Quantitative real-time PCR and lacZ assays showed that the point mutation resulted in 2-fold increased pps operon expression, which caused the increase in antifungal activity. Likewise, commercial Bacillus strains can be improved to display higher antifungal activity by rationally designed simple modifications of their genome, rendering them more efficient biocontrol agents.

• Journal of the Korean Magnetic Resonance Society
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• v.21 no.3
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• pp.78-84
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• 2017

Pseudin is a naturally occurring 24 amino-acid-residue antimicrobial peptide derived from the skin of paradoxical frog Pseud's paradoxa. It shows potency against the bacteria and antibiotic-resistant bacteria strain, but has high cytotoxicity against mammalian cell. In our previous study, substitution of $Pro^{11}$ for Gly (Ps-P) increased bacterial cell selectivity but decreased the antibacterial activity of pseudin. In this study, we designed pseudin analogue, Ps-4K-P with increased cationicity up to +7 in Ps-P by substituting Glu14, Gln10, Gln24, and Leu18 with Lys. Ps-4K-P showed improved potent antibacterial activity with high bacterial cell selectivity. We determined the tertiary structure of Ps-4K-P in the presence of DPC micelles by NMR spectroscopy and it has a hinge structure at $Pro^{11}$ followed by three turn helices from $Pro^{11}$ to $Val^{23}$ at the C-terminus. Amphipathicity with increased cationicity as well as helix-hinge-helix structural motif provided by introduction of a Pro at position $Gly^{11}$ are the crucial factors which confer antibacterial activity with bacterial cell selectivity to Ps-4K-P.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2883-2889
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• 2012

LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric antimicrobial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and ${\alpha}$-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis.

• Journal of Animal Science and Technology
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• v.63 no.3
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• pp.465-474
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• 2021

It has become important to explore alternative feed ingredients to reduce feed costs, which are burdensome for livestock production. In addition, it is desirable to find efficient and functional alternative ingredients for traditional feed ingredients in pig diets, considering the stress and sensitivity of disease of pig. Rice is produced around the world like corn that is the typical energy source in pig diets. Although the nutritional quality varies depending on the degree of milling, rice, except whole grains (paddy rice), contains more starch than corn and its structure and granule size are easier to digest than corn. In addition, the fact that rice has fewer non-starch polysaccharides (NSP) and anti-nutritional factors (ANFs) is also effective in improving digestibility and various polyphenols in rice can help modulation of immune responses, which can be beneficial to the gastrointestinal environment and health of pig. Many studies have been conducted on rice focusing on things such as degree of milling, substitution rates of corn, granule size, and processing methods. Most results have shown that rice can be partially or completely used to replace corn in pig diets without negatively affecting pig growth and production. While further research should focus on the precise biological mechanisms at play, it was confirmed that the use of rice could reduce the use of antibiotics and pig removal and protect pigs from gastrointestinal diseases including diarrhea. From this point of view, rice can be evaluated as a valuable feed ingredient for swine diets.

• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2002.10a
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• pp.18-25
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• 2002

The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.