• Tuberculosis and Respiratory Diseases
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• 제78권2호
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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.

• Archives of Pharmacal Research
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• 제24권2호
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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.

• 한국식품영양과학회지
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• 제24권5호
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• pp.779-784
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• 1995

5'-GMP(5'-Guanylic acid) 생산 융합균조 fusant RC102를 고정화하여 5'-GMP을 연속적으로 생산하고자 하였다. 균체 고정화용 담체로서 k-carrageenan, polyacrylamide, Ca-alginate 및 agar 등 4가지 담체에 고정화한 결과 최적 담체로서 3% k-carrageenan을 선정하였으며, 이담체에 고정화한 균체를 이용하여 5'-GMP 연속적으로 생산하였다. 고정화 균체에 의한 5'-GMP 생산의 최적 온도 및 pH은 $32^{\circ}C$, pH 8.0, 미량온소로서 $Mn^{2+}과\;Zn^{2+}$의 농도는 각각 $30\mu\textrm{g}/L,\;1{\times}10^{-6}%$이었다. $Mn^{2+}$이 풍부하고 값싼 CSL(Corn Steep Liquor)을 배지로서 사용하기 위해서 penicillin G와 D-cycloserine 및 POSEA(polyoxyethylene stearylamine) 농도 최적 농도는 각각 0.8unit/ml, 0.8unit/ml, 그리고 5mg/ml으로 나타났으며, 항생물질 보다 계면활성제가 효과적이었다. 이상의 최적 조건에서 고정화 fusant RC102는 15일간 안정되게 5'-GMP를 생산하였다.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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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• 제52권2호
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• pp.128-136
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• 2002

연구배경 : 다제내성 결핵 환자에서 fluoroquinolone계 약물이 빈번하게 처방되고 있음에도 불구하고, 이의 약동학적 특성에 대한 연구가 부족한 실정이다. 그러므로, 본 연구에서는 fluoroquinolone계 약물의 하나인 ofloxacin을 복용하고 있는 다제내성 결핵 환자에서의 ofloxacin의 약동학적 특성을 분석하였고, 아울러 ofloxacin의 약동학적 특성을 전신쇠약 상태와 연관지어 분석하였다. 방 법 : 300 mg b.i.d. 의 ofloxacin 용법을 포함하여 prothionamide, cycloserine, para-aminosalicylic acid, kanamycin 및 streptomycm 등의 2차 항결핵제제를 복용 중인 20명의 다제내성 결핵 환자를 대상으로 하였다. 전신쇠약 상태가 ofloxacin의 약동학에 미치는 영향을 평가하기 위하여 body mass indes (BMI)에 따라 환자를 두 군 (A 군 ; 18.5 $\leq$ BMI < 23, B군 : < 18.5)으로 나누어 두 군간의 ofloxacin의 항정상태 약동학적 특성을 비교분석하였다. 한 달 이상의 고정용법으로 항정상태에 이른 피험자에서 약동학 연구를 위하여 혈액을 경시적으로 13회 취하였고, 뇨 시료도 24 사간까지 취하였다. 혈장 및 뇨의 ofloxacin 농도를 HPLC를 이용하여 측정한 후 각각의 약동학적 분석을 시행하였다. 결 과 : Ofloxacin 의 AUC는 B군에서 $31.4{\pm}8.9{\mu}g/ml{\cdot}h$로 A군의 24.1+6.2 ${\mu}g/ml{\cdot}h$보다 유의하게 큰 것으로 나타났다(p<0.05). 항정상태에서 A군의 ofloxacin의 청소율 (Cl/F)은 $0.16{\pm}0.03$ L/h/kg로 산출되었고, B군에서는 $0.14{\pm}0.03$ L/h/kg로 나타났다. Ofloxacin의 반감기($t_{1/2}$)는 두 군간에 차이를 보이지 않았다(A군 : $5.3{\pm}0.8$시간, B군 $5.7{\pm}0.9$시간)으며 다른 약동학적 경수들도 두 군간의 유의한 차이를 보이지 않았다. 결 론 : 이상의 연구결과는 정상 피험자에 비하여 다제내성 결핵 환자에서 ofloxacin의 약동학적 특성이 유의하게 다르지 않음을 나타내고 있다. 한편, 만성 다제내성 결핵 환자의 전신쇠약 정도는 혈장 ofloxcaicn의 농도에 변화를 유발하는 것으로 기대된다.