• Title/Summary/Keyword: InhA

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Treatment of Isoniazid-Resistant Pulmonary Tuberculosis (Isoniazid 내성 폐결핵의 치료실태와 치료성적)

  • Koh, Won-Jung;Kwon, O Jung;Yu, Chang-Min;Jeon, Kyeongman;Kim, Kyung Chan;Lee, Byoung-Hoon;Hwang, Jung Hye;Kang, Eun Hae;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.248-260
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    • 2004
  • Background : As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. Materials and Methods : Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. Results : A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. Conclusions : Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.

An Experimental Study on the metabolism of 5-Hydroxytryptamine (5-Hydroxytryptamine 代謝에 관한 實驗的 硏究)

  • Hah, Jae Chung;Lee, Wuen Ho
    • The Korean Journal of Zoology
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    • v.16 no.1
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    • pp.13-23
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    • 1973
  • The changes in the quantitative distribution and in cytoplasmic granules of tongue mast cells and duodenal enterochromaffin cells in male albino rats were observed following oral administration of 40mg/kg body wt. isonicotinic acid hydraside (INH) and 20mg/kg body wt. pyridoxine. The results obtained are summarized as follows: 1. INH administered-rat showed a marked decrease in the number of mast cells, caused by leakage of cytoplasmic granules, while pyridoxine-rat showed increased the number of mast cells. 2. Similarly, INH-rat showed a marked decrease in the number of enterochromaffin cells. In the case of pyridoxine-rat, however, the number of enterochromaffin cells increased compared with that of the controls. 3. In view of the fact that a large dose of INH was harmful to the formation of mast cells and enterochromaffin cells. And considering that a moderate dose of pyridoxine stimulated the formation of the two kinds of cells and the amounts of cytoplasmic granules, it was concluded that pyridoxine might be concerned with the metabolism of secretory products, 5-Hydroxytryptamine.

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Effect of C1 Esterase Inhibitor on the Cardiac Dysfunction Following Ischemia and Reperfusion in the Isolated Perfused Rat Heart

  • Lee, Geon-Young;Shin, Yong-Kyoo;Jang, Yoon-Young;Song, Jin-Ho;Kim, Dae-Joong
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.6
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    • pp.579-586
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    • 1999
  • Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement- dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs $(100{\times}10^6)$ and homologous plasma improved coronary flow and preserved cardiac contractile function (p<0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p<0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

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Spore Display Using Bacillus thuringiensis Exosporium Protein InhA

  • Park, Tae-Jung;Choi, Soo-Keun;Jung, Heung-Chae;Lee, Sang-Yup;Pan, Jae-Gu
    • Journal of Microbiology and Biotechnology
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    • v.19 no.5
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    • pp.495-501
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    • 2009
  • A new spore display method is presented that enables recombinant proteins to be displayed on the surface of Bacillus spores via fusion with InhA, an exosporium component of Bacillus thuringiensis. The green fluorescent protein and $\beta$-galactosidase as model proteins were fused to the C-terminal region of InhA, respectively. The surface expression of the proteins on the spores was confirmed by flow cytometry, confocal laser scanning microscopy, measurement of the enzyme activity, and an immunogold electron microscopy analysis. InhA-mediated anchoring of foreign proteins in the exosporium of Bacillus spores can provide a new method of microbial display, thereby broadening the potential for novel applications of microbial display.

Treatment of Isoniazid-Resistant Pulmonary Tuberculosis

  • Jhun, Byung Woo;Koh, Won-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.1
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    • pp.20-30
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    • 2020
  • Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

Performance of the BD MAX MDR-TB assay in a clinical setting and its impact on the clinical course of patients with pulmonary tuberculosis: a retrospective before-after study

  • Sung Jun Ko;Kui Hyun Yoon;Sang Hee Lee
    • Journal of Yeungnam Medical Science
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    • v.41 no.2
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    • pp.113-119
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    • 2024
  • Background: Missing isoniazid (INH) resistance during tuberculosis (TB) diagnosis can worsen the outcomes of INH-resistant TB. The BD MAX MDR-TB assay (BD MAX) facilitates the rapid detection of TB and INH and rifampin (RIF) resistance; however, data related to its performance in clinical setting remain limited. Moreover, its effect on treatment outcomes has not yet been studied. Methods: We compared the performance of BD MAX for the detection of INH/RIF resistances to that of the line probe assay (LPA) in patients with pulmonary TB (PTB), using the results of a phenotypic drug sensitivity test as a reference standard. The treatment outcomes of patients who used BD MAX were compared with those of patients who did not. Results: Of the 83 patients included in the study, the BD MAX was used for an initial PTB diagnosis in 39 patients. The sensitivity of BD MAX for detecting PTB was 79.5%. The sensitivity and specificity of BD MAX for INH resistance were both 100%, whereas these were 50.0% and 95.8%, respectively, for RIF resistance. The sensitivity and specificity of BD MAX were comparable to those of LPA. The BD MAX group had a shorter time interval from specimen request to the initiation of anti-TB drugs (2.0 days vs. 5.5 days, p=0.001). Conclusion: BD MAX showed comparable performance to conventional tests for detecting PTB and INH/RIF resistances. The implementation of BD MAX as a diagnostic tool for PTB resulted in a shorter turnaround time for the initiation of PTB treatment.

Prevalence of Drug-resistances in Patients with Pulmonary Tuberculosis and Its Association with Clinical Characteristics at One Tertiary Referral Hospital in Pusan, Korea (부산지역 한 3차 병원으로 내원한 폐결핵 환자에서 약제 내성률과 예측인자간의 연관성)

  • Son, Choon-Hee;Yang, Doo-Kyung;Rho, Mee-Sook;Jeong, Jin-Sook;Lee, Hyuck;Lee, Ki-Nam;Choi, Pil-Jo;Lee, Soo-Keol;Chang, Kwang-Yul;Choi, Ik-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.5
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    • pp.416-425
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    • 2001
  • Background : The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. Methods : The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. Results : The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently associated with a history of previous treatment(odds ratio; 9.43, 9.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio; 2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio; 4.17 and 4.81 respectively, p<0.05). Conclusion : This study revealed that patients with a prior treatment history for pulmonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.

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Hepatotoxicity of Rifampicin and Pyrazinamide Treatment Excluding Isoniazid (Isoniazid를 제외한 Rifampicin과 Pyrazinamide 병합치료의 간독성 빈도)

  • Choi, Ik Su;Park, I-Nae;Hong, Sang-Bum;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Shim, Tae Sun
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.1
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    • pp.38-43
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    • 2006
  • Background : Even though two-month rifampicin (RMP, R) and pyrazinamide (PZA, P) treatment has some advantages over isoniazid (INH, H) treatment for latent tuberculosis infection (LTBI), it was withdrawn from the list of treatment regimens for LTBI because of reported cases of severe hepatotoxicity. The purpose of this study was to estimate the frequency of hepatotoxicity of RMP and PZA treatment excluding INH in a Korean population. Method : TIn order to recruit patients who were prescribed RMP and PZA excluding INH, 256 INH-resistant tuberculosis patients were investigated through retrospective medical record analysis. A standard four-drug regimen was changed to a RMP/PZA-containing regimen excluding INH in 64 patients (RZ+ group). In the same study period, 146 patients who were prescribed an INH/RMP/PZA-containing standard regimen were randomly selected as a control (HRZ+ group). Clinical characteristics including liver diseases and the frequency of drug-induced hepatitis were compared between the RZ+ and HRZ+ groups. Result : The mean age of patients in the RZ+ group was 50.2 (${\pm}16.2$) and the male-to-female ratio was 36:28. The frequency of underlying liver diseases was 10.9% (7/64), which was not significantly different from that of the HRZ+ group (4.1%, 6/146). Even though the treatment duration of RZ+ ($5.5{\pm}4.8months$) was longer that than that of HRZ+ ($2.7{\pm}2.3months$), the frequency of toxic hepatitis was not significantly different between RZ+ and HRZ+ groups, 3.5% (2/57) and 7.1% (10/140), respectively. Conclusion : Hepatotoxicity was mild and occurred in a minor proportion of patients in a Korean population prescribed an RMP/PZA-containing regimen. A future prospective study including more patients is needed.

The Preventive Effect of 5-Iodo-6-Amino-1,2-Benzopyrone on Apoptosis of Rat Heart-derived Cells induced by Oxidative Stress

  • Kyoumg A Chung;Ji Seung Back;Jae Hyun Jang
    • Biomedical Science Letters
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    • v.28 no.4
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    • pp.237-246
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    • 2022
  • Ischemia-reperfusion results in excess reactive oxygen species (ROS) that affect myocardial cell damage. ROS production inhibition is effectively proposed in treating cardiovascular diseases including myocardial hypertrophy. Studies have shown that oxidizing cultured cells in in vitro experiments gradually decreases the permeability of mitochondrial membranes time- and concentration-dependent, resulting in increased mitochondrial membrane damage due to secondary ROS production and cardiolipin loss. However, recent studies have shown that 5-iodo-6-amino-1,2-benzopyrone (INH2BP), an anticancer and antiviral drug, inhibited peroxynitrite-induced cell damage in in vitro and alleviated partial or overall inflammation in animal experiments. Therefore, in this paper, we studied the preventive effect of INH2BP on H9c2 cells derived from mouse heart damaged by oxidative stress using 700 μM of hydrogen peroxide. As a result of oxidative stress to H9c2 cells by hydrogen peroxide whether the treatment of INH2BP or not, hydrogen peroxide caused serious damage in H9c2 cells. These results were confirmed with cell viability and Hoechst 33342 assays. And this damage was through cell death. However, it was confirmed that H9c2 cells pretreated with INH2BP significantly reduced cell death by hydrogen peroxide. In addition, measurements with DCF-DA assay to determine whether ROS is produced in H9c2 cells treated with only hydrogen peroxide produced ROS significantly, but H9c2 cells pretreated with INH2BP significantly reduced ROS production by hydrogen peroxide. Taken together, it is believed that INH2BP can be useful for the prevention and treatment of cardiovascular diseases induced through oxidative stress such as heart damage caused by ischemia/reperfusion.

Synergistic Effect of Azadirachta Indica Extract and Iodide Ions on the Corrosion Inhibition of Aluminium in Acid Media (Azadirachta Indica엑스와 요드화이온이 산성매체에서 Al 부식방지에 대한 Synergistic 효과)

  • Arab, S.T.;Al-Turkustani, A.M.;Al-Dhahiri, R.H.
    • Journal of the Korean Chemical Society
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    • v.52 no.3
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    • pp.281-294
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    • 2008
  • synergistic action caused by iodide ions on the corrosion inhibition of aluminium (Al) in 0.5 M HCl in the presence of Azadirachta Indica (AZI) plant extract has been investigated using potintiodynamic polarization and impedance techniques. It is found that AZI extract inhibits the corrosion of aluminium in 0.5 M HCl. The inhibition efficiency increases with the increase in AZI extract concentration, until 24% v/v of AZI extract, then Inh.% is decreased with father increase in AZI extract concentration. The adsorption of this extract in the studied concentration is found to obey Frewendlish adsorption isotherm. The addition of iodide ions enhances the inhibition efficiency to a considerable extent. The increase in Inh.% values in presence of fixed concentration of iodide ions indicates that AZI extract forms an insoluble complex at lower AZI extract concentrations by undergoing a joint adsorption. But at higher concentrations of AZI extract, competitive adsorption is found between iodide ions and the formed complex leading to less Inh.%.The Inh.% decreased in presence of iodide ions with AZI extract than in presence of AZI extract alone at all studied iodide concentrations. The synergism parameter Sq is defined and calculated from surface coverage values. This parameter in the case of AZI extract is found to be more than unity, indicating that the enhanced inhibition efficiency caused by the addition of iodide ions.