• Journal of Preventive Medicine and Public Health
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• v.52 no.1
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• pp.66-70
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• 2019

Objectives: In the Republic of Korea (ROK), the notified incidence of tuberculosis in foreign-born individuals (NITFBI) has increased recently, as has the rate of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis in foreigners staying in the ROK. As Jeju Province in ROK has a no-visa entry policy, control programs for NITFBI should be consolidated. The aim was to evaluate the status of NITFBI, with a focus on the distribution of MDR/RR tuberculosis by nationality. Methods: Data on tuberculosis incidence in individuals born in Jeju Province and in foreign-born individuals were extracted from the Korean Statistical Information Service of Statistics Korea, and the Infectious Disease Surveillance Web Statistics of the Korea Centers for Disease Control and Prevention, respectively. Results: Among all notified incident cases of tuberculosis, the proportion of NITFBI increased from 1.46% in 2011 to 6.84% in 2017. China- and Vietnam-born individuals accounted for the greatest proportion of the 95 cases of NITFBI. Seven cases of MDR/RR tuberculosis were found, all involving patients born in China. Conclusions: In Jeju Province, ROK, NITFBI might become more common in the near future. Countermeasures for controlling active tuberculosis in immigrants born in high-risk nations for tuberculosis should be prepared in Jeju Province, since it is a popular tourist destination.

• Journal of the Korean Chemical Society
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• v.56 no.2
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• pp.236-245
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• 2012

The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.

• Archives of Plastic Surgery
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• v.41 no.6
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• pp.759-767
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• 2014

Background Infection caused by nontuberculous mycobacteria (NTM) has been increasing. Awareness of this infection is crucial yet problematic. Delayed management may lead to destructive results. We empirically treated a series of patients with clinical suspicion of NTM infection prior to the identification of the pathogen. Methods A total of 12 patients who developed surgical site infections between January 2011 and February 2014 were reviewed. Patients with a skin and subcutaneous infection resistant to standard management over two weeks, and previous history of aesthetic procedures within three months were regarded as highly suspected of having an NTM infection. A variety of diagnostic modalities were examined simultaneously, along with starting empirical treatment including a combination of clarithromycin and moxifloxacin, and surgical debridement. Results All wounds healed completely within 4 weeks. The mean follow-up duration was 7.2 months, and none of the patients developed relapse. Specific NTM pathogens were identified in six patients. Eight patients showed caseating granuloma implying an NTM infection. One patient showed an uncommon Stenotrophomonas infection, which was successfully treated. Three patients had no evidence of a pathogen despite repeated microbial tests. Complications such as scarring, pigmentation, and disfigurement were common in all the patients. Conclusions NTM should be considered in the differential diagnosis of an unusual skin and soft-tissue infection. We propose an empirical regimen of clarithromycin and moxifloxacin as an efficient treatment option for an NTM infection.

• Journal of Microbiology and Biotechnology
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• v.27 no.11
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• pp.1932-1941
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• 2017

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to $0.39{\mu}g/ml$, DFC-2 inhibited both drugusceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2's action in M. tuberculosis. The most affected functional gene category was "lipid biosynthesis," which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.26-33
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• 2006

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.6-12
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• 2018

The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB-those with frequent exposure to active TB cases, and those with clinical risk factors (e.g., immunocompromised patients). Recently revised National Institute for Health and Care Excellence (NICE) guideline recommended that close contacts of individuals with active pulmonary or laryngeal TB, aged between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI treatment were recommended in NICE, World Health Organization (WHO), and Centers for Disease Control and Prevention guidelines, and superiority of one recommended regimen over another was not yet established. Traditional 6 to 9 months of isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for clinical efficacy-60%-90% of estimated protective effect. However, 6H or 9H regimen is related with hepatotoxicity and low compliance. Four months of rifampin regimen is characterized by less hepatotoxicity and better compliance than 9H, but has few evidence of clinical efficacy. Three months of isoniazid plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy and safety, which was recommended in NICE and WHO guidelines. The clinical efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was demonstrated recently, which is not yet introduced into South Korea.

• BMB Reports
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• v.40 no.6
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• pp.911-920
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• 2007

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the leading infectious diseases to humans. It is urgent to discover novel drug targets for the development of antitubercular agents. The 2-C-methyl-Derythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has been considered as an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammals. MEP cytidyltransferase (IspD), the third-step enzyme of the pathway, catalyzes MEP and CTP to form 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) and PPi. In the work, ispD gene from M. tuberculosis H37Rv (MtIspD) was cloned and expressed. With N-terminal fusion of a histidine-tagged sequence, MtIspD could be purified to homogeneity by one-step nickel affinity chromatography. MtIspD exists as a homodimer with an apparent molecular mass of 52 kDa. Enzyme property analysis revealed that MtIspD has high specificity for pyrimidine bases and narrow divalent cation requirements, with maximal activity found in the presence of CTP and $Mg^{2+}$. The turnover number of MtIspD is $3.4 s^{-1}$. The Km for MEP and CTP are 43 and $92{\mu}M$, respectively. Furthermore, MtIspD shows thermal instable above $50^{\circ}C$. Circular dichroism spectra revealed that the alteration of tertiary conformation is closely related with sharp loss of enzyme activity at higher temperature. This study is expected to help better understand the features of IspD and provide useful information for the development of novel antibiotics to treat M. tuberculosis.

• Investigative Magnetic Resonance Imaging
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• v.13 no.2
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• pp.146-151
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• 2009

Purpose : To evaluate magnetic resonance (MR) imaging features of non-surgically treated tuberculous spondylitis and to evaluate the relationships between these features and clinical outcomes. Materials and Methods : Data from ten patients (male:female=6:4, mean age=45 years) with clinically proven tuberculous spondylitis who were treated nonsurgically over three months were analyzed retrospectively from 2000 to 2007. MRI was performed at least three times for each patient, at baseline, every three or six months, and at the end of treatment. All images were analyzed by two radiologists. Results : The mean follow-up period for the MR examination was 10.1 months (range, 4-17 months). Six patients had clinically complete resolution of tuberculous spondylitis with medication treatment only. Four patients were treated with surgical management alongside medication. All ten patients were divided into two groups by clinical outcome; six patients with complete treatment and four patients with incomplete treatment. In the complete treatment group, follow-up MR findings showed a loss of subligamentous spread of abscesses, decreased size of abscesses, no interval changes in vertebral body heights, and fatty changes in spinal lesions. MR findings in the incomplete treatment group showed bone marrow edema extension to adjacent vertebra, extension of the abscesses, and decreased height of the vertebral bodies. Conclusion : During the nonsurgical management of tuberculous spondylitis, MR imaging may play a role in predicting patient response to antituberculous drug treatment.

• Tuberculosis and Respiratory Diseases
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• v.64 no.6
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• pp.427-432
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• 2008

Background: A paradoxical response is defined as the radiological and clinical worsening of a previous lesion or the development of new lesion after initial improvement during theprocess of antituberculous treatment. The related factors for the development of a paradoxical response in patients with tuberculous pleurisy are not certain. Methods: We selected patients with tuberculous pleurisy who had been treated for more than 4 months. The changes onthe serial chest X-ray findings before and after treatment were reviewed. Paradoxical responses were regarded as any worsening or development of new lesion at least 2 weeks after the initiation of treatment. The baseline clinical characteristics and laboratory findings of the peripheral blood and pleural fluid were compared between the patients with a paradoxical response and the patients without a paradoxical response. Results: Paradoxical responses appeared in sixteen patients (21%) among the 77 patients.It took a mean of 38.6 days after the treatment and the time to resolve the paradoxical response was a mean of 32.1 days. For the patients with a paradoxical response, the median age was younger (30.5 years vs 39.0 years, respectively) and the lymphocytic percentage of white blood cells in the pleural fluid was higher (82.1% vs 69.6%, respectively) than for the patients without a paradoxical response. Conclusion: The development of a paradoxical response during the treatment of patients with tuberculous pleurisy was not rare and this was related with the age of the patients and the percentage of lymphocytic white blood cells in the pleural fluid.