• Journal of Microbiology and Biotechnology
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• v.24 no.11
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• pp.1464-1472
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• 2014

The microbial community structures of two continuous stirred tank reactors digesting turkey manure with pine wood shavings as well as chicken and swine manure were investigated. The reactor fed with chicken/swine wastes displayed the highest organic acids concentration (up to 15.2 g/l) and ammonia concentration (up to 3.7 g/l ammonium nitrogen) and generated a higher biogas yield (up to $366ml/g_{VS}$) compared with the reactor supplied with turkey wastes (1.5-1.8 g/l of organic acids and 1.6-1.7 g/l of ammonium levels; biogas yield was up to $195ml/g_{VS}$). The microbial community diversity was assessed using both sequencing and profiling terminal restriction fragment length polymorphisms of 16S rRNA genes. Additionally, methanogens were analyzed using methyl coenzyme M reductase alpha subunit (mcrA) genes. The bacterial community was dominated by members of unclassified Clostridiales with the prevalence of specific clostridial phylotypes in each reactor, indicating the effect of the substrate type on the community structure. Of the methanogenic archaea, methanogens of the genus Methanosarcina were found in high proportions in both reactors with specific methanosarcinas in each reactor, whereas the strict hydrogenotrophic methanogens of Methanoculleus sp. were found at significant levels only in the reactor fed with chicken/swine manure (based on the analyses of 16S rRNA gene). This suggests that among methanogenic archaea, Methanosarcina species which have different metabolic capabilities, including aceticlastic and hydrogenotrophic methanogenesis, were mainly involved in anaerobic digestion of turkey wastes.

• Journal of Microbiology and Biotechnology
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• v.21 no.7
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• pp.766-775
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• 2011

We investigated the effect of high molecular weight polygamma- glutamic acid (hm ${\gamma}$-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm ${\gamma}$-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm ${\gamma}$-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm ${\gamma}$-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm ${\gamma}$-PGA. In agreement with observations in animal study, the supplementation of hm ${\gamma}$-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm ${\gamma}$-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm ${\gamma}$-PGA on cholesterol levels in rats and humans.

• Health Policy and Management
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• v.24 no.2
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• pp.120-127
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• 2014

Background: Since December 2010, online computerized prospective drug utilization review (pDUR) has been implemented in Korea. pDUR involves the review of each prescription before the medication is dispensed to the individual patient. The pDUR is performed electronically by Health Insurance Review & Assessment Service (HIRA), which is a Korean governmental agency, and then HIRA provides medical institutions and pharmacies with information that can be helpful to them in preventing potential drug problems such as drug/drug interactions or ingredient duplication. The aim of this study was to assess the impact of the Korean pDUR implementation on the proportion of drug-drug interactions (DDIs) using claims data from HIRA. Methods: A before-after comparison of the prevalence of DDIs between prescription was conducted, using HIRA administrative claims data of medical institution from January 2010 to December 2011. The analysis unit was the prescription issued and pairs before and after. The main outcome measures were the proportion of DDIs within- (control group) or between- physician encounters. To examine the difference, a paired t-test was applied. Results: We found that DDIs proportion between prescription decreased significantly (t=3.04, p=0.0026) after the implementation of pDUR, whereas there is no significant reduction within prescription (t=1.15, p=0.2518). With respect to the prevalence of DDIs between drug groups, the most dramatic reduction was occurred between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and anti-fungal agents. Conclusion: It seems effective that giving a direct feedback to prescribers by a prospective DUR. Further research is needed to assess the impact of DUR to final outcomes such as hospitalization.

• BMB Reports
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• v.39 no.1
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• pp.46-54
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• 2006

The coenzyme A-acylating 2-oxoacid:ferredoxin oxidoreductase and ferredoxin (an effective electron acceptor) were purified from the hyperthermophilic archaeon, Sulfolobus solfataricus P1 (DSM1616). The purified ferredoxin is a monomeric protein with an apparent molecular mass of approximately 11 kDa by SDS-PAGE and of $11,180{\pm}50$ Da by MALDI-TOF mass spectrometry. Ferredoxin was identified to be a dicluster, [3Fe-4S][4Fe-4S], type ferredoxin by spectrophotometric and EPR studies, and appeared to be zinc-containing based on the shared homology of its N-terminal sequence with those of known zinc-containing ferredoxins. On the other hand, the purified 2-oxoacid: ferredoxin oxidoreductase was found to be a heterodimeric enzyme consisting of 69 kDa $\alpha$ and 34 kDa $\beta$ subunits by SDS-PAGE and MALDI-TOF mass spectrometry. The purified enzyme showed a specific activity of 52.6 units/mg for the reduction of cytochrome c with 2-oxoglutarate as substrate at $55^{\circ}C$, pH 7.0. Maximum activity was observed at $70^{\circ}C$ and the optimum pH for enzymatic activity was 7.0 -8.0. The enzyme displays broad substrate specificity toward 2-oxoacids, such as pyruvate, 2-oxobutyrate, and 2-oxoglutarate. Among the 2-oxoacids tested (pyruvate, 2-oxobutyrate, and 2-oxoglutarate), 2-oxoglutarate was found to be the best substrate with $K_m$ and $k_{cat}$ values of $163\;{\mu}M$ and $452\;min^{-1}$, respectively. These results provide useful information for structural studies on these two proteins and for studies on the mechanism of electron transfer between the two.

• Journal of Life Science
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• v.28 no.4
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• pp.472-477
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• 2018

Pravastatin sodium is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia by reducing cholesterol biosynthesis. Pharmaceutical excipients of commonly used including water, diluents, stabilizers, disintegrants, lubricants and colorants, and were identified for compatibility. All tests were performed by means of physical mixture of pravastatin and the excipients, which were placed in a press-through-pack (PTP) and incubated under accelerated conditions ($40^{\circ}C$ and 75% relative humidity) for 3 months. The blends of pravastatin with all excipients developed white, off white, and light brown powders, which showed no changes upon visual analysis. Accelerated conditions changed the degradation profile of pravastatin calcium in the HPLC system when mixed with different excipients. Although most excipients can have minor effects on pravastatin stability, the major degradation product from pravastatin was lactone. Low-level interaction (assay and impurity) was induced by all excipients except for microcrystalline cellulose and croscarmellose sodium. These excipients increased lactone impurity in 3 months by as much as 0.22% and 0.18% respectively. The total mixture slightly increased the lactone impurity (by 0.43% in 3 months) of pravastatin. There was no change in the assays of all excipients. These results will be helpful in studying tablet size reductions for convenience of use.

• Plant Biotechnology Reports
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• v.5 no.1
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• pp.53-60
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• 2011

Artemisinin is effective against both chloroquine-resistant and -sensitive strains of Plasmodium species. However, the low yield of artemisinin from cultivated and wild plants is a serious limitation to the commercialization of this drug. Optimization of artemisinin yield either in vivo or in vitro is therefore highly desirable. To this end, we have overexpressed the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) gene (hmgr) from Catharanthus roseus L. in Artemisia annua L. and analyzed its influence on artemisinin content. PCR and Southern blot analyses revealed that the transgenic plants showed stable integration of the foreign hmgr gene. The reverse transcriptase-PCR results suggested that the hmgr was expressed at the transcriptional level in transgenic lines of Artemisia annua L., while the high-performance liquid chromatography analysis showed that artemisinin content was significantly increased in a number of the transgenic lines. Artemisinin content in one of the A. annua transgenic lines was 38.9% higher than that in non-transgenic plants, and HMGR enzyme activity in transgenic A. annua L. was also higher than that in the non-transgenic lines.

• Toxicological Research
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• v.31 no.2
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• pp.173-180
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• 2015

Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

• Journal of Microbiology and Biotechnology
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• v.14 no.3
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• pp.576-583
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• 2004

GERI-155 is a macrolide antibiotic containing two deoxyhexose molecules and shows antimicrobial activities against Gram-positive bacteria. Deoxysugar biosynthetic gene cluster of GERI-155 from Streptomyces sp. GERI-l55 genome was cloned. Four orfs were identified and a putative orf presumed to be the dTDP g]ucose-4,6-dehydratase gene was designated as gerE. GerE was expressed in E. coli by using a recombinant expression vector pHJ1. The expressed protein was purified from E. coli cell lysate by using ammonium sulfate fractionation, and DEAE-sepharose CL-6B and hydroxylapatite column chromatography. The molecular mass of the expressed protein correlated with the predicted mass that was deduced from the cloned gene sequence data. The recombinant protein was a homodimer with a subunit relative molecular weight of 39,000 Dalton. It was found to have dTDP-glucose 4,6-dehydratase activity and also found to be highly specific for dTDP-glucose as a substrate. The values of $K_{m} and V_{max}$ for dTDP-g]ucose were $32\mu$M and 335 nmol $min^{-1}$ (mg protein)^{-1}$, respectively. dTTP and dTDP were strong inhibitors of the protein. $NAD^+$, the coenzyme for dTDP-glucose 4,6-dehydratase, was tightly bound to the expressed protein.

• Annals of dermatology
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• v.30 no.6
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• pp.676-687
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• 2018

Background: Rosacea is associated with chronic systemic disease. However, research is lacking in Asian countries. Objective: To evaluate the association between rosacea and cardiovascular diseases (CVDs) related systemic comorbidities, and the use of antihypertensive and antihyperlipidemic drugs in Korea. Methods: A five-year retrospective study, using hospital database, was conducted in five medical centers for five years. Totally 1,399,528 patients were evaluated. Results: The overall frequency for diagnosed rosacea was 0.18% over five years (2,536 rosacea patients). Patients with diabetes and patients with dyslipidemia were more likely to have rosacea (odd ratio [OR] 2.724, 95% confidence interval [CI] 1.295~5.730, p=0.016; OR 1.788, 95% CI 1.445~2.212, p<0.001). Patients with CVD were less likely to have rosacea (OR 0.431, 95% CI 0.244~0.760, p=0.003). Patients with ${\alpha}$-blocker prescriptions and patients with ${\beta}$-blocker prescriptions showed a tendency diagnosed with rosacea frequently (OR 1.963, 95% CI 1.200~3.212, p=0.006; OR 3.939, 95% CI 3.512~4.419, p<0.001). Patients with [beta]-hydroxy-[beta]-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and those with fibrate, were prone to have rosacea (OR 1.599, 95% CI 1.390~1.839, p<0.001; OR 1.660, 95% CI 1.056~2.609, p=0.026). As adjusted results, among the patients who took HMG-CoA reductase inhibitor without dyslipidemia, rosacea was less likely to be diagnosed (OR 0.780, 95% CI 0.620~0.982, p=0.034). Conclusion: Rosacea is associated with chronic diseases and drugs.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.24-31
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• 2013

Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.