• Tuberculosis and Respiratory Diseases
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• 제41권3호
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• pp.302-306
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• 1994

A 33-year old male was admitted due to continuous high spiking fever for 2 months via local clinic. He had been diagnosed pulmonary tuberculosis at local clinic. However, spiking fever had not been controlled by anti-tuberculous medications. Chest PA showed confluent consolidation on right upper & mid-lung field. 5 anti-tuberculous regimens(Streptomycin, Isoniazid, Rifampin, Ethambutol, Pyrazinamaide) were administered initially and steroid therapy was followed for relieving toxic symptoms Very slowly resolved chest X-ray lesion and continuous fever suggested the possibility of misdiagnosis. After 60th hospital day, the chest X-ray lesion was resolved gradually and fever subsided almost completely. He was discharged on 76th hospital day with anti-tuberculous drugs and steroid(prednisolon), without any other problems except sustained mild fever.

• Genomics & Informatics
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• 제12권4호
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• pp.276-282
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• 2014

The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.854-858
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• 2005

A Lactobacillus isolate was collected from the feces of a healthy Korean individual and named as Lactobacillus ruminus SPM0211. It was further characterized by subjecting it to an antibiotic resistance test and genetic analysis. In the antibiotic resistance test, all tested Lactobacillus spp. were classified as 'high resistance' for multiple antibiotics, such as isoniazid, ethambutol, cycloserine, and vancomycin. L. ruminus SPM0211 was classified as 'high resistance' for streptomycin also, while the other tested Lactobacillus spp. were classified as low resistance. This suggests that the antimicrobial spectra may be a good indicator in the discrimination of this strain among the tested Lactobacillus spp. In a polymerase chain reaction-random amplified polymorphic DNA (PCR-RAPD) analysis using the Microbial Uniprimer kit, L. ruminus SPM0211, and L. suebicus were clustered as a group with a 74.3% similarity level, suggesting that these two species are genetically related. Thus, our data suggest that the PCR-RADP method using the Microbial Uniprimer kit may be valuable in discriminating L. ruminus SPM0211 from other Lactobacillus spp.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.450-456
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• 2019

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine's effect on anxiety. For the characterization of potential mechanism of taurine's anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine's anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.111-121
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• 2022

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.479-492
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• 1997

연구배경 : Isoniazid(INH)와 Rifampicin(RFP)은 강력한 항결핵효과를 가지고 있어 결핵치료에 없어서는 안되는 중요한 약제이지만 우리나라에서는 미국흉부학회에서 추천하는 용량과 다른 용량을 흔히 처방하면서도 적절한 용량에 대한 평가는 미흡하여 결핵의 치료에 혼선을 초래하고 있는 실정이다. 이에 저자들은 정상 한국인에서의 INH, RFP 각각의 약물동력학을 먼저 알아보고, INH 300mg과 INH 400mg복용시, RFP 450mg과 600mg복용시 약통학(pharmacokinetics)적 변화를 비교 분석함으로써 한국인에서 INH, RFP 처방의 기초자료로 제공하고자 본 연구를 시행하였다. 방 법 : 정상인 자원자 22명을 12시간 이상 금식시킨 후 INH 300mg을 복용하게 한 다음, 시간경과에 따른 INH 혈중농도 및 INH 뇨배설량을 High-performance liquid chromatography(HPLC)를 이용하여 측정하였다. 2주후 동일인을 대상으로 INH 400mg을 복용시킨 다음 같은 방법으로 INH 혈중농도 및 뇨배설량을 측정하였다. 마찬가지 방법으로 자원자 20명을 대상으로 RFP 450mg과 600mg을 2주 간격으로 복용시킨 다음, 시간경과에 따른 RFP 혈중농도 및 뇨배설량을 측정하였다. 이 결과를 토대로 최고혈중농도(peak serum concentration, Cmax), 최고혈중농도 도달시간(time to reach to peak serum concentration, Tmax), 혈중반감기, 소실속도상수(elimination rate constank, Ke), 전신 클리어런스(total clearance, CLtot), 신 클리어런스(renalclearance, CLr) 및 신외 클리어런스(nonrenal clearance, CLnr)를 계산하여 비교하였으며, paired t-test로 p value < 0.05 일 경우 통계적으로 의미있는 차이가 있는 것으로 판정하였다. 결 과 : 1) INH 결과 ㄱ) Tmax는 INH 300mg군이 $1.05{\pm}0.34$시간, INH 400mg군이 $0.98{\pm}0.59$시간으로서 두 군간에 차이가 없었고(p > 0.05), 혈중반감기도 INH 300mg군이 $2.49{\pm}0.88$시간, INH 400mg 군이 $2.80{\pm}0.75$시간으로서 두 군간에 차이는 없었다(p>0.05). ㄴ) Cmax는 INH 300mg군이 $4.37{\pm}1.28mcg/mL$, INH 400mg군이 $7.14{\pm}1.95mcg/mL$로서 INH 400mg군에서 유의하게 높았지만(p < 0.01), Ke는 각각 $0.30{\pm}0.07hrs^{-1}$, $0.27{\pm}0.11hrs^{-1}$로서 차이가 없었다(p < 0.05). ㄷ) CLtot은 INH300mg군이 $26.76{\pm}11.80mL/hr$, INH 400mg군이 $21.09{\pm}8.31 mL/hr$로서, INH 400mg군에서 유의하게 낮았다(p < 0.01). 이중 CLr은 각각 $3.04{\pm}1.68mL/hr$, $2.91{\pm}0.77mL/hr$로서 두 군간에 차이가 없었으나(p>0.05), CLnr은 각각 $23.71{\pm}11.52mL/hr$, $18.18{\pm}8.36mL/hr$로서 INH 400mg군에서 유의하게 낮았다(p<0.01). 2) RFP결과 ㄱ) Tmax는 RFP 450m군이 $1.11{\pm}0.41$시간, RFP 600mg군이 $1.15{\pm}0.43$시간으로서 두 군간에 차이가 없었고(> 0.05), 혈중반감기도 RFP 450mg군이 $4.20{\pm}0.73$시간, RFP 600mg군이 $4.95{\pm}2.25$ 시간으로서, 두 군간에 유의한 차이는 없었다(p > 0.05). ㄴ) Cmax는 RFP 450mg군이 $10.12{\pm}2.25mcg/mL$, RFP 600mg군이 $13.61{\pm}3.43mcg/mL$로서 RFP 600mg군에서 유의하게 높았고(p < 0.01), Ke도 각각 $0.17{\pm}0.03hrs^{-1}$, $0.15{\pm}0.03hrs^{-1}$로서 RFP 600mg군에서 통계적으로 유의하게 낮았다(p < 0.01). ㄷ) CLtot은 RFP 450mg군이 $7.60{\pm}1.34mL/hr$, RFP 600mg군이 $7.05{\pm}1.20mL/hr$로서, RFP 600mg군에서 유의하게 낮았다(p < 0.05). 이중 CLr은 각각 $1.41{\pm}0.65mL/hr$, $1.69{\pm}0.61mL/hr$로서 두 군간에 차이가 없었으나(p>0.05), CLnr은 각각 $6.19{\pm}1.56mL/hr$, $5.36{\pm}1.26mL/hr$로서 RFP 600mg군에서 유의하게 낮았다(p < 0.01). 결 론 : 한국인에서는 INH는 300mg이, RFP은 450mg이 적절한 일일용량으로 생각되나 이는 향후 복합적으로 결핵약을 복용하는 실제 결핵환자를 대상으로 한 추시가 필요할 것으로 생각된다.

• 대한화학회지
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• 제56권2호
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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.

• Tuberculosis and Respiratory Diseases
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• 제76권5호
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• pp.245-248
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• 2014

Miliary tuberculosis (TB) is a rare extrapulmonary form of TB, and there have been only two reports of miliary TB associated with infection with multidrug-resistant (MDR)-TB pathogen in an immunocompetent host. A 32-year-old woman was referred to our hospital because of abnormal findings on chest X-ray. The patient was diagnosed with MDR-TB by a line probe assay and was administered proper antituberculous drugs. After eight weeks, a solid-media drug sensitivity test revealed that the pathogen was resistant to ethambutol and streptomycin in addition to isoniazid and rifampicin. The patient was then treated with effective antituberculous drugs without delay after diagnosis of MDR-TB. To the best of our knowledge, this is the first case of miliary TB caused by MDR-TB pathogen in Korea.

• 대한미생물학회지
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• 제17권1호
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• pp.87-93
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• 1982

Two cases of pulmonary disease in a 54 year-old female and a 70 year-old male patient due to Mycobacterium avium-intracellulare complex(MAIC) and a case of pulmonary infection ina 69 year-old male patient due to M. fortuitum(MF) were found recently in this institute. All three patients had a long history of anti-tuberculous chemotherapy because they were initially diagnosed as pulmonary tuberculosis. A 70 year-old male patient infected with MAIC had an unsuccessful chemotherapy history of isoniazid(INH), para-aminosalicylic acid(PAS) and streptomycin(SM) with an incomplete, temporary, symptomatic improvement, for three years since 1964 when he was first diagnosed as pulmonary tuberculosis on physical examination. A 54 year-old female patient infected with MAIC also had an unsuccessful chemotherapy history with the various anti-tuberculous drugs since 1958. Both patients discharged large number of MAIC in their sputum specimens for at least more than one year, but no M. tuberculosis at all. A 69 year-old male patient infected with MF was diagnosed as moderately advanced pulmonary tuberculsis in 1977. Combined chemotherapy with INH+PAS+pyrazinamide(PZA) improved his clinical symptoms, however, his chest radiograph was deteriorated again in 1980 one year after he stopped therapy. Therefore he started chemotherapy again with INH+ethionamide(TH)+cycloserine(CS) but no improvement was noticed. MF was cultured from his sputum in August 1981 and he continuously discharged the same bacilli until last examination of January 1982. Whether all three patients were initially !infected with nontuberculous mycobacteria or complicated with predisposing tuberculosis was not clear because there were no reliable bacteriological examination records.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제17권4호
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• pp.456-461
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• 1995

저자들은 좌측 악하부의 종창을 주소로 내원한 48세 여자 환자에서 임상소견과 방사선 검사 및 절제생검 조직의 병리조직학적 검사를 통해 폐의 일차적 결핵병소 없이 발생한 결핵성 경부 임파선염으로 진단하고 절제생검과 술후 isoniazid, rifampin, ethambutol을 이용한 화학요법을 시행하여 양호한 결과를 치험하였다. 비록 흔하지는 않지만 특히 젊은 성인에서 경부에 종괴가 있을 경우 감별진단시에 결핵성 경부 임파선염을 고려해야 하며, 이 질환은 재발의 가능성이 있기 때문에 주기적인 관찰과 검사가 필요할 것으로 생각된다.