• KSBB Journal
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• v.11 no.2
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• pp.132-139
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• 1996

The growth of recombinant E. coil and by-product production were investigated. D-cycloserine was added to increase the secretion of ${\alpha}$-amylase from recombinant E.coil. Even though cell growth was increased for optimal d-cycloserine concentration $0.1g/\ell$, extracellular ${\alpha}$-amylase activity remained almost the same as the case without d-cycloserine. It is important to achieve the high cell density for commercial production of methaboliles including ${\alpha}$-amylase. To achieve this goal, culture conditions should be selected carefully and optimized considering cell growth and by-products production. In cultivating retombinant E. coli, lactic acid and acetic acid turned out to be important by-product which affected cell yield and growth rate.

• Archives of Pharmacal Research
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• v.9 no.3
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• pp.163-167
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• 1986

Twenty six urea analogues, most of which have already been approved for human use, were tested for their antiurease activity in vitro. Cell-free extracts obtained from a clinical isolate of Proteus mirabilis was used as the source of enzyme. Acetohydroxamic acid which is a proven potent urease inhibitor but not approved for human use was again shown to be the most active compound among the tested. Phenacemide, cycloserine, and deferoxamine were demonstrated to be moderate inhibitors. Oxtetracycline, trimethoprim, and cefamandole revealed a demonstrable antiruease activity, but only at very high concentrations. The antiurease activity of cycloserine, trimethoprim, and cefamandole was pH dependent-only active at acidic pH. The inhibitory activity of acetohydroxamic acid however was independent of change in pH. The inhibitory activity of acetohydroxamic acid however was independent of change in pH. Hydrogen ion concentration plays an important role in urease activity and acidification (pH 5. 5) alone eliminates approximately 65% of the enzymic activity. Adjustment of pH therefore appears to be an important adjunct in reducing unrease activity and should always be studied to maximize the effcacy of antiurease compounds under investigation.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.167-171
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• 1992

Background:In the management of patients whose primary chemotherapy has failed, very careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow-up of 112 smear positive cases, who were treated by four-drug regimen between July 1985 and June 1990. Four drugs were, namely prothionamide, cycloserine, para-aminosalicylic acid, and streptomycin (kanamycin or tuber-actinomycin). The duration of follow-up was over one year. Results: 1) Out of 112 cases with positive sputum AFB smear, 72 (64%) achieved the negative conversion. 2) Among the 72 patients, 85% achieved negative conversion within 3 months after treatment. 3) When the duration of patient's illness was less than 2 years, 2 to 4 years and more than 5 years, the favourable response to retreatment was 86%, 62% and 54%, respectively. 4) When the number of sensitive drugs was 4,3,2 and 1, the favourable response rate was 74%, 68%, 39% and 0%, respectively. Conclusion: The shorter the duration of patient's illness was, the larger the number of sensitive drugs was. And the larger the number of sensitive drugs was, the better the result of treatment was. Thus it is very crucial to successfully treat newly discovered patients with adequate regimens and proper case-holding.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.136-143
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• 2001

Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a result of fumonisin exposure is related to cell death (Yoo et al., 1992). The objective of this study was to investigate whether elevated free sphinganine levels are related to the sensitivity of cultured cells to fumonisin exposure. Fumonisin $B_1$ elevated the intracellular free sphinganine concentraions in both LLC-$PK_1$ and Chinese hamster ovary (CHO) cells. However, CHO cells are resistant to fumonisin cytotoxicity at 50${u}m$, while LLC-$PK_1$ cells are sensitive at concentrations greater than 357M. The intracellular concentration of free sphinganine in LLC-$PK_1$ cells treated at 50${u}m$ fumonisin $B_1$ for 72 h was approximately 1450 pmol/mg protein relative to the 37 pmol observed in the control culture. Under the same conditions, the population of apoptotic cells in the 50${u}m$ fumonisin $B_1$-treated culture was approximately 37% of the total compared to 12% in the control. The caspase III-like activity after 72 h in the 50${\mu}$M fumonisin $B_1$-exposed culture Increased to approximately 50 $pmol/mg$ protein/hr compared to 6 $pmol/mg$ protein/hr in the control. L-cycloserine, a serine palmitoyltransferase inhibitory reduced the fumonisin $B_1$-stimulated caspase III-like activity down to the control level. Under the same culture conditions, the intracellular concentration of free sphinganine after-cycloserine plus fumonisin $B_1$ treatment was 140 pmol/mg protein compared to 1450 $pmol/mg$ protein in fumonisin $B_1$ alone. The intracellular concentration of free sphinganine in CHO cells treated with 50${u}m$ fumonisin $B_1$ for 72 h was al)proximately 460 pmol/mg protein, indicating that the mass amount of elevated free sphinganine in the CHO cells was about 32% of that in LLC-$PK_1$ cells. Adding exogenous sphinganine to the CHO cells along with 50${u}m$ fumonisin $B_1$ treatment for 72 h caused both necrosis and apoptosis. In conclusion, the elevated endogenous sphinganine acts as a contributing factor to the fumonisin-induced cell death.

• Journal of Microbiology and Biotechnology
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• v.4 no.3
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• pp.235-236
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• 1994

Direct colony hybridization on agarose gel plate was established for the identification of recombinant plasmids. The hybridization of the probe to nucleic acids on dried gel without transferring to solid supports was more effective and simpler than hybridization of such probes to materials immobilized on filters such as nitrocellulose or nylon. D-cycloserine in overlaying agamse was essential for releasing the nucleic acids from colony.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.5
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• pp.779-784
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• 1995

The effective production of 5'-GMP(5'-Guanylic acid) by immobilized 5'-GMP producing fusant RC102(intergeneric protoplast fusion between Brevibacterium ammoniagenes ATCC21263 and Corynebacterium glutamicum ATCC21171) was investigated. The Fusant RC102 was immobilized by entrapping in -carrageenan, agar, polyacrylamide or Ca-alginate. 3% k-carrageenan was selected as the most suitable matrix. In the production of 5'-GMP using the immobilized whole cells of fusant RC102, the optimum conditions were $32^{\circ}C$, pH 8.0, $30\mu\textrm{g}/L\;of\;Mn^{2+},\;1{\times}10^{-6}%\;of\;Zn^{2+}$. In order to use fermentation medium containing CSL(Corn Steep Liquor) plentiful in $Mn^{2+}$, the optimum conditions of penicillin G, D-cycloserine and POESA(polyoxyethylene stearylamine) for production of 5'-GMP were 0.8unit/ml, 0.8unit/ml, 0.8unit/ml and 5mg/ml, respectively. Cationic surfactant, POESA was effective and superior to the antibiotics, penicillin G or D-cyloserine in 5'-GMP productivity. The condinuous fermentation using immobilized fusant RC102 showed that 5'-GMP productivity was stable for more than 15 days.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.78-84
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• 2015

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.295-301
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• 1995

Background: The serious problems in retreatment of pulmonary tuberculosis are a significant proportion of drug resistance. Preferably retreatment should contain the drugs which has never used before, so drug retreatment is limited in selection. A new antibacterial substance, ofloxacin(OFX) is the activity against mycobacterium tuberculosis and it has been used in the treatment of pulmonary tuberculosis. The present report concerns the result of retreatment of pulmonary tuberculosis patients containing OFX treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow up of 92 smear positive cases, who were treated by four drugs regimen between Mar 1991 and June 1994 at National Kongju Tuberculosis Hospital. Four drugs were, namely prothionamide, cycloserine, ofloxacin and streptomycin(kanamycin or tuberactinomycin). The duration of follow up was over one year. Results: 1) Out of 92 cases with positive sputum AFB smear, 67(73%) achieved the negative conversion. 2) Considering the negative sputum conversion in all the groups, the vast majority(85%) of sputum conversion occurred within the first 4 months. 3) The roentgenological improvement occurred in 49 percent on the whole and when the extent of disease was minimal, moderately, far advanced pulmonary tuberculosis, sputum AFB smear negative response to retreatment was 100%, 93%, 68%, respectively. 4) When the duration of patient's illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 87%, 76%, 65% and 55%, respectively. 5) Adverse reaction to prothionamide, with complaints of gastrointestinal troubles was common and hepatic dysfunction without jaundice was observed in 7 percent, convulsion in 1 percent, that to cycloserine occurred renal dysfunction & psycosis & convulsion, 2%, 1%, 1%, respectively. Tinnitus with KM occurred in 1% and dirrhea with OFX in 4%. Conclusion: The duration of patient's illness was shorter, sputum AFB smear negative response rate was better. Radiologic responses were not remarkable, but extent of disease by national tuberculosis association was smaller, the result of retreatment was better. Adverse reaction of the secondary antituberculosis agent was mainly observed gastrointestinal troubles, as regard to tolerance to the secondary drugs the role of the physician is of very important value and toxic effects can be overcome by the strong confidence.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.279.1-279.1
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• 2002

Accumulation of ceramide mass in MCF-7 cells by the anti-cancer agent. paclitaxel. was found to occur primarily due to activation of the de novo synthesis pathway. Morever. the addition of paclitaxel resulted in the accumulation of ceramide, which was followed by a prolonged arachidonic acid release. Participation of ceramide de novo pathway in arachidonate signaling was detected since L-cycloserine, an inhibitor of de novo synthesis, was able to inhibit the paclitaxel-induced AA release and cytotoxicity. (omitted)

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.693-700
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• 1996

Background : Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drugs involving OFX. Method : A retrospective study was made through the regular follow up of smear positive cases,who treated by four drug, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(pAS). Results: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78%, 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the drnation of patients illness was less than 1 year, 1 to 3 years, 3 10 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52 %. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). Conclusion : The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.