• 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.

• 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 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.

• Archives of Pharmacal Research
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• v.28 no.7
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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.

• 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.52 no.2
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• pp.128-136
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• 2002

Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.