Indexed In : Science Citation Index Expanded(SCIE), MEDLINE,
Pubmed/Pubmed Central, Elsevier Bibliographic, Google Scholar,
Databases(Scopus & Embase), KCI, KoreaMed, DOAJ
Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
The remaining articles are usually sent to two reviewers. It would be very helpful if you could suggest a selection of reviewers and include their contact details. We may not always use the reviewers you recommend, but suggesting reviewers will make our reviewer database much richer; in the end, everyone will benefit. We reserve the right to return manuscripts in which no reviewers are suggested.
The final responsibility for the decision to accept or reject lies with the editors. In many cases, papers may be rejected despite favorable reviews because of editorial policy or a lack of space. The editor retains the right to determine publication priorities, the style of the paper, and to request, if necessary, that the material submitted be shortened for publication.
Jun-Won Chung1, Su Young Kim1, Hee Jung Park2, Chang Su Chung1, Hee Woo Lee1, Sun Mi Lee3, Inki Kim3, Jhang Ho Pak3, Gin Hyug Lee2, Jin-Yong Jeong3
Correspondence to: Jin-Yong Jeonga and Gin Hyug Leeb. aDepartment of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea, Tel: +82-2-3010-4105, Fax: +82-2-3010-4182, E-mail: jyjeong@amc.seoul.kr. bDepartment of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea, Tel: +82-2-3010-3197, Fax: +82-2-485-5782, E-mail: jhlee409@chollian.net
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gut Liver 2017;11(5):648-654. https://doi.org/10.5009/gnl16503
Published online July 28, 2017, Published date September 15, 2017
Copyright © Gut and Liver.
The increased resistance of We screened a small molecule library—the library of pharmacologically active compounds (LOPAC), which includes 1,280 pharmacologically active compounds—to identify inhibitors of We identified diphenyleneiodonium (DPI) as a novel anti- DPI may be a candidate anti-Background/Aims
Methods
Results
Conclusions
Keywords:
To improve first-line treatments for
Various methods have recently been introduced to overcome the drawbacks of four-drug treatment and fluoroquinolone-containing therapy. Rifabutin-containing therapy, probiotics, and tailored therapy are alternative methods.10,11 However, these methods involve some challenges. Rifabutin causes serious complications, such as myelosuppression, and is difficult to use in countries with a high incidence of
The library of pharmacologically active compounds (LOPAC) is a collection of high-quality innovative molecules, such as antibiotics, enzyme inhibitors, cell-cycle regulators, and various other substances. It is designed for the identification of novel drug discovery assay and commonly used for screening of novel agents in drug discovery fields. LOPAC includes a large number of small molecules, and small molecules have certain benefits, such as high chemical stability and simple synthesis. Additionally, small molecules registered with LOPAC are commercially available and their effects on human cells are well known. Therefore, it is easier to apply these substances in clinical practice. Many studies have demonstrated that LOPAC is useful and effective for detecting new drugs against various pathogens, such as fungi, tuberculosis, malaria, and viruses.17–20 Therefore, we utilized LOPAC as a way to identify anti-
The well-characterized ATCC 43504
The LOPAC Chemical Library was purchased from Sigma-Aldrich Co. and is composed of 1,280 small pharmacologically active molecules. These chemical compounds (2 mM) were serially diluted in 96-well source plates to select the growth inhibition concentration in a 50-μL volume. Each well of the 96-well microplate contained 180 μL of culture medium to which 10 μL of the chemical compound and 10 μL of a stock solution of 106
The susceptibilities of the
More than 50 chemical compounds from the small-molecule LOPAC library prevented any visible
We further evaluated the possible anti-
The activity of DPI against common gram-negative and -positive pathogenic bacteria was also assessed. The MIC results are indicated in Table 2 and ranged between 0.5 and 2 μg/mL against gram-negative bacteria. The MIC of DPI against all of the tested gram-positive bacteria was 1 μg/mL. These MIC values are comparable to those of vancomycin, which is a commonly used antibiotic against gram-positive bacteria including methicillin-resistant
We demonstrate that the NADPH oxidase inhibitor DPI has inhibitory activities against reference and resistant
DPI is likely to be a novel agent in the future for two reasons. First, a NADPH oxidase inhibitor is a new substance that has never been used to treat
As mentioned earlier, the rate of resistance to commonly used antibiotics such as clarithromycin, metronidazole, and fluoroquinolone is the main cause of the decrease in the eradication rate of certain bacteria. In addition, the number of multidrug-resistant bacterial strains has increased. This highlights a critical need to develop selective antibacterial agents with novel target sites and establish an effective drug-resistance management strategy. In contrast, the development of new antimicrobial agents is somewhat out of proportion. Rifabutin, furazolidone, sitafloxacin, and nitazoxanide have been introduced but are not always available in some countries. In addition, rifabutin demonstrates serious side effects, such as myelosuppression, and should be reserved to treat mycobacterial infections. Furazolidone is a nitrofuran antibiotic that has demonstrated efficacy in some trials. However, it has been recognized by the U.S. Food and Drug Administration as a carcinogenic agent and thus is no longer used, except in a few developing countries.33 Sitafloxacin seems to be effective, but clinical data are still limited in Japan.34,35 Nitazoxanide is an antiprotozoal agent that has demonstrated efficacy in a restricted study, but it is a somewhat expensive agent.36,37 Further studies of these antibiotics are needed.
In addition to these antimicrobial approaches, therapeutic alternatives beyond antibiotics have been investigated in recent years, including natural phytotherapy and probiotics.22,38 Representative agents include
Acid stability is an important factor for antibiotics used to treat
We demonstrated that DPI has the ability to strongly eradicate
In conclusion, DPI shows a potent MIC value against
This work was supported by a grant from the Asan Institute for Life Sciences (number: 2013-348, Asan Medical Center, Seoul, Korea) and Il-Yang Pharmaceutical (GCU 2014–5115).
Antimicrobial Susceptibilities of the Tested
Strain | Resistance | MIC, μg/mL | ||||
---|---|---|---|---|---|---|
CLA | AMO | MET | LEV | DPI | ||
HP43504 | MET | 0.03 | <0.03 | 128 | 0.25 | <0.03 |
CS_S1 | - | 0.03 | 0.125 | 4 | 0.25 | <0.03 |
CS_S2 | - | 0.03 | 0.125 | 4 | 0.25 | <0.03 |
CS_S3 | - | 0.03 | <0.03 | 2 | 0.25 | <0.03 |
CS_C1 | CLA | 64 | 0.25 | 4 | 0.5 | <0.03 |
CS_C2 | CLA | 32 | 0.125 | 4 | 0.5 | <0.03 |
CS_C3 | CLA | 64 | <0.03 | 2 | 0.25 | <0.03 |
CS_M1 | MET | 0.06 | <0.03 | 128 | 0.5 | <0.03 |
CS_M2 | MET | 0.06 | <0.03 | 128 | 0.5 | <0.03 |
CS_M3 | MET | 0.06 | 0.125 | 128 | 0.5 | <0.03 |
CS_L1 | LEV | 0.03 | 0.25 | 2 | 16 | <0.03 |
CS_L2 | LEV | 0.06 | 0.125 | 2 | 32 | <0.03 |
CS_L3 | LEV | 0.06 | <0.03 | 4 | 8 | <0.03 |
CS_A1 | AMO | 0.06 | 1 | 4 | 0.25 | <0.03 |
CS_A2 | AMO | 0.06 | 2 | 4 | 0.25 | <0.03 |
CS_A3 | AMO | 0.03 | 4 | 4 | 0.25 | <0.03 |
CS_CM1 | CLA/MET | 32 | <0.03 | 128 | 0.5 | <0.03 |
CS_CM2 | CLA/MET | 64 | <0.03 | 16 | 0.25 | <0.03 |
CS_CM3 | CLA/MET | 32 | 0.03 | 64 | 0.25 | <0.03 |
CS_CA1 | CLA/AMO | 64 | 1 | 2 | 0.25 | <0.03 |
CS_CA2 | CLA/AMO | 64 | 1 | 4 | 0.25 | <0.03 |
CS_CA3 | CLA/AMO | 32 | 2 | 1 | 0.25 | <0.03 |
CS_CML | CLA/MET/LEV | 128 | 0.06 | 128 | 64 | <0.03 |
CS_CMA | CLA/MET/AMO | 64 | 1 | 64 | 0.5 | <0.03 |
Antimicrobial Susceptibility of Gram-Negative and Gram-Positive Pathogenic Bacteria to DPI and Vancomycin
Strain | MIC, μg/mL | ||
---|---|---|---|
DPI | Vancomycin | ||
Gram-positive | 1 | 1 | |
1 | 1 | ||
1 | 4 | ||
1 | 2 | ||
Gram-negative | 0.5 | >32 | |
2 | >32 | ||
1 | >32 | ||
1 | >32 | ||
1 | >32 | ||
1 | >32 |
Gut and Liver 2017; 11(5): 648-654
Published online September 15, 2017 https://doi.org/10.5009/gnl16503
Copyright © Gut and Liver.
Jun-Won Chung1, Su Young Kim1, Hee Jung Park2, Chang Su Chung1, Hee Woo Lee1, Sun Mi Lee3, Inki Kim3, Jhang Ho Pak3, Gin Hyug Lee2, Jin-Yong Jeong3
1Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea, 2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 3Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Correspondence to: Jin-Yong Jeonga and Gin Hyug Leeb. aDepartment of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea, Tel: +82-2-3010-4105, Fax: +82-2-3010-4182, E-mail: jyjeong@amc.seoul.kr. bDepartment of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea, Tel: +82-2-3010-3197, Fax: +82-2-485-5782, E-mail: jhlee409@chollian.net
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The increased resistance of We screened a small molecule library—the library of pharmacologically active compounds (LOPAC), which includes 1,280 pharmacologically active compounds—to identify inhibitors of We identified diphenyleneiodonium (DPI) as a novel anti- DPI may be a candidate anti-Background/Aims
Methods
Results
Conclusions
Keywords:
To improve first-line treatments for
Various methods have recently been introduced to overcome the drawbacks of four-drug treatment and fluoroquinolone-containing therapy. Rifabutin-containing therapy, probiotics, and tailored therapy are alternative methods.10,11 However, these methods involve some challenges. Rifabutin causes serious complications, such as myelosuppression, and is difficult to use in countries with a high incidence of
The library of pharmacologically active compounds (LOPAC) is a collection of high-quality innovative molecules, such as antibiotics, enzyme inhibitors, cell-cycle regulators, and various other substances. It is designed for the identification of novel drug discovery assay and commonly used for screening of novel agents in drug discovery fields. LOPAC includes a large number of small molecules, and small molecules have certain benefits, such as high chemical stability and simple synthesis. Additionally, small molecules registered with LOPAC are commercially available and their effects on human cells are well known. Therefore, it is easier to apply these substances in clinical practice. Many studies have demonstrated that LOPAC is useful and effective for detecting new drugs against various pathogens, such as fungi, tuberculosis, malaria, and viruses.17–20 Therefore, we utilized LOPAC as a way to identify anti-
The well-characterized ATCC 43504
The LOPAC Chemical Library was purchased from Sigma-Aldrich Co. and is composed of 1,280 small pharmacologically active molecules. These chemical compounds (2 mM) were serially diluted in 96-well source plates to select the growth inhibition concentration in a 50-μL volume. Each well of the 96-well microplate contained 180 μL of culture medium to which 10 μL of the chemical compound and 10 μL of a stock solution of 106
The susceptibilities of the
More than 50 chemical compounds from the small-molecule LOPAC library prevented any visible
We further evaluated the possible anti-
The activity of DPI against common gram-negative and -positive pathogenic bacteria was also assessed. The MIC results are indicated in Table 2 and ranged between 0.5 and 2 μg/mL against gram-negative bacteria. The MIC of DPI against all of the tested gram-positive bacteria was 1 μg/mL. These MIC values are comparable to those of vancomycin, which is a commonly used antibiotic against gram-positive bacteria including methicillin-resistant
We demonstrate that the NADPH oxidase inhibitor DPI has inhibitory activities against reference and resistant
DPI is likely to be a novel agent in the future for two reasons. First, a NADPH oxidase inhibitor is a new substance that has never been used to treat
As mentioned earlier, the rate of resistance to commonly used antibiotics such as clarithromycin, metronidazole, and fluoroquinolone is the main cause of the decrease in the eradication rate of certain bacteria. In addition, the number of multidrug-resistant bacterial strains has increased. This highlights a critical need to develop selective antibacterial agents with novel target sites and establish an effective drug-resistance management strategy. In contrast, the development of new antimicrobial agents is somewhat out of proportion. Rifabutin, furazolidone, sitafloxacin, and nitazoxanide have been introduced but are not always available in some countries. In addition, rifabutin demonstrates serious side effects, such as myelosuppression, and should be reserved to treat mycobacterial infections. Furazolidone is a nitrofuran antibiotic that has demonstrated efficacy in some trials. However, it has been recognized by the U.S. Food and Drug Administration as a carcinogenic agent and thus is no longer used, except in a few developing countries.33 Sitafloxacin seems to be effective, but clinical data are still limited in Japan.34,35 Nitazoxanide is an antiprotozoal agent that has demonstrated efficacy in a restricted study, but it is a somewhat expensive agent.36,37 Further studies of these antibiotics are needed.
In addition to these antimicrobial approaches, therapeutic alternatives beyond antibiotics have been investigated in recent years, including natural phytotherapy and probiotics.22,38 Representative agents include
Acid stability is an important factor for antibiotics used to treat
We demonstrated that DPI has the ability to strongly eradicate
In conclusion, DPI shows a potent MIC value against
This work was supported by a grant from the Asan Institute for Life Sciences (number: 2013-348, Asan Medical Center, Seoul, Korea) and Il-Yang Pharmaceutical (GCU 2014–5115).
Table 1 Antimicrobial Susceptibilities of the Tested
Strain | Resistance | MIC, μg/mL | ||||
---|---|---|---|---|---|---|
CLA | AMO | MET | LEV | DPI | ||
HP43504 | MET | 0.03 | <0.03 | 128 | 0.25 | <0.03 |
CS_S1 | - | 0.03 | 0.125 | 4 | 0.25 | <0.03 |
CS_S2 | - | 0.03 | 0.125 | 4 | 0.25 | <0.03 |
CS_S3 | - | 0.03 | <0.03 | 2 | 0.25 | <0.03 |
CS_C1 | CLA | 64 | 0.25 | 4 | 0.5 | <0.03 |
CS_C2 | CLA | 32 | 0.125 | 4 | 0.5 | <0.03 |
CS_C3 | CLA | 64 | <0.03 | 2 | 0.25 | <0.03 |
CS_M1 | MET | 0.06 | <0.03 | 128 | 0.5 | <0.03 |
CS_M2 | MET | 0.06 | <0.03 | 128 | 0.5 | <0.03 |
CS_M3 | MET | 0.06 | 0.125 | 128 | 0.5 | <0.03 |
CS_L1 | LEV | 0.03 | 0.25 | 2 | 16 | <0.03 |
CS_L2 | LEV | 0.06 | 0.125 | 2 | 32 | <0.03 |
CS_L3 | LEV | 0.06 | <0.03 | 4 | 8 | <0.03 |
CS_A1 | AMO | 0.06 | 1 | 4 | 0.25 | <0.03 |
CS_A2 | AMO | 0.06 | 2 | 4 | 0.25 | <0.03 |
CS_A3 | AMO | 0.03 | 4 | 4 | 0.25 | <0.03 |
CS_CM1 | CLA/MET | 32 | <0.03 | 128 | 0.5 | <0.03 |
CS_CM2 | CLA/MET | 64 | <0.03 | 16 | 0.25 | <0.03 |
CS_CM3 | CLA/MET | 32 | 0.03 | 64 | 0.25 | <0.03 |
CS_CA1 | CLA/AMO | 64 | 1 | 2 | 0.25 | <0.03 |
CS_CA2 | CLA/AMO | 64 | 1 | 4 | 0.25 | <0.03 |
CS_CA3 | CLA/AMO | 32 | 2 | 1 | 0.25 | <0.03 |
CS_CML | CLA/MET/LEV | 128 | 0.06 | 128 | 64 | <0.03 |
CS_CMA | CLA/MET/AMO | 64 | 1 | 64 | 0.5 | <0.03 |
MIC, minimal inhibitory concentration; CLA, clarithromycin; AMO, amoxicillin; MET, metronidazole; LEV, levofloxacin; DPI, diphenyleneiodonium; HP,
Table 2 Antimicrobial Susceptibility of Gram-Negative and Gram-Positive Pathogenic Bacteria to DPI and Vancomycin
Strain | MIC, μg/mL | ||
---|---|---|---|
DPI | Vancomycin | ||
Gram-positive | 1 | 1 | |
1 | 1 | ||
1 | 4 | ||
1 | 2 | ||
Gram-negative | 0.5 | >32 | |
2 | >32 | ||
1 | >32 | ||
1 | >32 | ||
1 | >32 | ||
1 | >32 |
DPI, diphenyleneiodonium; MIC, minimal inhibitory concentration; MSSA, methicillin-sensitive