• Journal of Microbiology and Biotechnology
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• 제23권3호
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• pp.430-435
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• 2013

Multidrug resistance, especially multidrug efflux mechanisms that extrude structurally unrelated cytotoxic compounds from the cell by multidrug transporters, is a serious problem and one of the main reasons for the failure of therapeutic treatment of infections by pathogenic microorganisms as well as of cancer cells. Streptococcus mutans is considered one of the primary causative agents of dental caries and periodontal disease, which comprise the most common oral diseases. A fragment of chromosomal DNA from S. mutans KCTC3065 was cloned using Escherichia coli KAM32 as host cells lacking major multidrug efflux pumps. Although E. coli KAM32 cells were very sensitive to many antimicrobial agents, the transformed cells harboring a recombinant plasmid became resistant to several structurally unrelated antimicrobial agents such as tetracycline, kanamycin, rhodamin 6G, ampicillin, acriflavine, ethidium bromide, and tetraphenylphosphonium chloride. This suggested that the cloned DNA fragment carries a gene encoding a multidrug efflux pump. Among 49 of the multidrug-resistant transformants, we report the functional gene cloning and characterization of the function of one multidrug efflux pump, namely MdeA from S. mutans, which was expressed in E. coli KAM32. Judging from the structural and biochemical properties, we concluded that MdeA is the first cloned and characterized multidrug efflux pump using the proton motive force as the energy for efflux drugs.

• Journal of Ginseng Research
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• 제34권3호
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• pp.183-191
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• 2010

Dry mouth is easily neglected if not associated with oral diseases. Consequently, xerostomatic patients often use unconventional therapies. In traditional Korean medicine, Korean red ginseng (KRG) has long been used to relieve dry mouth. However, no clinical trials have investigated whether KRG actually has an effect on dry mouth. This study was performed to evaluate the efficacy of KRG for dry mouth. We enrolled 100 volunteers with no obvious oral or salivary gland diseases and divided them into KRG and placebo groups. Each group was divided into six subgroups according to age and gender. The subjects received 6 g/day of KRG or placebo for 8 weeks. The dry mouth visual analog scale (VAS), salivary flow rate, and a dry mouth-related symptom questionnaire were evaluated at baseline and at 4 and 8 weeks. KRG treatment did not show any significant differences for any of the variables. However, KRG improved the dry mouth VAS at 4 weeks and dry mouthrelated symptoms at 8 weeks in women, but not in men. Subgroup analyses revealed that KRG markedly improved the dry mouth VAS in women of menopausal age (40 to 59 years) at 4 and 8 weeks. KRG may have beneficial effects for dry mouth in women, especially those of menopausal age, but not in men. Further investigation in post- and perimenopausal women is required to elaborate on these findings.

• Advances in Traditional Medicine
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• 제4권4호
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• pp.267-273
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• 2004

Oxidative stress is associated with many kinds of chronic diseases. Antioxidants such as polyphenols are compounds that protect cells against the damaging effects of reactive oxygen species. Grape seeds are considered good resources of polyphenols, and grape seed extracts have a very strong antioxidant effect. In the present study, we established a simple gradient reverse-phase high performance liquid chromatography method to determine polyphenol content from three different grape seed resources. An ODS (2), $150\;{\times}\;3.2\;mm$ column has been employed, and six polyphenols have been determined: gallic acid, protochatechuic acid, (+)-catechin, (-)-epicatechin, procyanidin B2, and epicatechin gallate. Catechin and epicatechin were the main polyphenol compounds in all three extracts. The amount of procyanidin B2 was higher in Extract 1 (from a company of China), while Extract 2 (extracted in our lab) and Extract 3 (from a company of USA) contained higher proportions of epicatechin gallate. For the total polyphenol content, Extract 1 was much higher than that of Extract 2 and 3. The results suggest that the dietary dose of grape seed extracts from different resources should be adjusted according to polyphenol content.

• 대한수의학회지
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• 제45권1호
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• pp.131-137
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• 2005

To assess anesthetic depth using quantitative electroencephalography (q-EEG), we recorded processed EEG (raw EEG) till 100 minutes in beagle dogs anesthetized for 60 minutes with tiletamine/zolazepam (n=5, TZ group), xylazine/ketamine (n=5, XK group) and propofol (n=5, PI group) by intermittent bolus injection. Raw EEG was converted into 95% spectral edge frequency (SEF) and median frequency (MF) through fast fourier transformation (FFT) method. 95% SEF value of TZ group was significantly higher (p<0.05) than the XK group from 10 minutes to 100 minutes. 95% SEF value of PI group was significantly higher (p<0.05) than the XK group from 10 minutes to 40 minutes, and significantly low (p<0.05) than XK group at 90 and 100 minutes. MF was significantly higher (p<0.05) in TZ group from 60 minutes to 100 minutes. Based on these results, using dissociative agent with ${\alpha}_2$-adrenergic agent is more potent in CNS depressed than using dissociative agent alone, and low doses of propofol has a disinhibitory effect on CNS.

• Clinical and Experimental Reproductive Medicine
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• 제40권4호
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• pp.155-162
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• 2013

Objective: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. Methods: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 ${\mu}g/rat$). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. Results: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. Conclusion: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.

• 대한화장품학회지
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• 제25권2호
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• pp.59-75
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• 1999

Skin is continuously exposed to external stimuli including ultraviolet radiation, which is a major cause of skin photoaging. According to recent discoveries, UVA with a lower energy but deep-penetrating properties, compared to UVB, is likely to play a major part in causing skin photoaging. The clinical and histochemical changes of photoaging are well characterized, but the biochemical mechanisms are poorly understood partly due to the lack of suitable experimental systems. In this work, three-dimensional, reconstituted skin culture models were prepared. After certain period of maturation, the equivalent models were shown to be similar in structure and biochemical characteristics to normal skin. Mature dermal and skin equivalent models were exposed to sub-lethal doses of UVA, and the effects of UVA relevant to dermal photoaging were monitored, including the production of elastin, collagen, collagenase(MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1). Interestingly, dermal and skin equivalents reacted differently to acute and chronic exposure to UVA. Elastin production was increased as soon as one week after commencing UVA irradiation by chronic exposure, although a single exposure failed to do so. This early response could be an important advantage of equivalent models in studying elastosis in photoaged skin. Collagenase activity was increased by acute UVA irradiation, but returned to control levels after repeated exposure. On the other hand, collagen biosynthesis, which was increased by a single exposure, decreased slightly during 5 weeks of prolonged UVA exposure. Collagenase has been thought to be responsible for collagen degeneration in dermal photoaging. However, according to the results obtained in this study, elevated collagenase activity is not likely to be responsible for the degeneration of collagen in dermal photoagig, while reduced production of collagen may be the main reason. It can be concluded that reconstituted skin culture models can serve as useful experimental tools for the study of skin photoaging. These culture models are relatively simple to construct, easy to handle, and are reproducible Moreover the changes of dermal photoaging can be observed within 1-4 weeks of exposure to ultraviolet light compared to 4 months to 2 years for human or animal studies. These models will be useful for biochemical and mechanistic studies in a large number of fields including dermatology, toxicology, and pharmacology.

• 약학회지
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• 제49권1호
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• pp.30-37
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• 2005

Xuesaitong Ruanjiaonang (XR), a soft capsule containing Panax notoginseng saponins as main ingredients, is believed to remove extravasated blood and increase cerebral blood flow by improving blood circulation, and therefore, has been used in China to treat ischemic stroke or hemiplegia caused by cerebral thrombosis. To characterize pharmacological actions of XR, the present study evaluated its effects on neuronal cell damage induced by various oxidative insults or excitotoxic amino acids in primary cultured rat cortical cells. The neuronal cell viability was not affected by XR with the exposure for 2 h at the concentrations tested in this study ($10{\sim}1000\;{\mu}g/ml$). However, significant reduction of the cell viability was observed when the cultured cells were exposed to XR at $1000\;{\mu}g/ml$ for 24 h. XR was found to concentration-dependently inhibit the oxidative neuronal damage induced by $H_{2}O_2$, xanthine/xanthine oxidase or $Fe^{2+}$/ascorbic acid. In addition, it dramatically inhibited the excitotoxic damage induced by glutamate or N-methyl-D-aspartate (NMDA). We found that the NMDA-induced neurotoxicity was inhibited more effectively and potently than the glutamate-induced toxicity. Moreover, XR was found to exert mild inhibition of lipid peroxidation induced by $Fe^{2+}$/ascorbic acid in rat brain homogenates and some 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate neuroprotective and antioxidant effects of XR, showing inhibition of oxidative and excitotoxic damage in the cultured cortical neurons, as well as inhibition of lipid peroxidation and its radical scavenging activity. Considering that excitotoxicity and oxidative stress pl ay crucial roles in neuronal cell damage during ischemia and reperfusion, these results may provide pharmacological basis for its clinical usage to treat ischemic stroke.

• 약학회지
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• 제54권2호
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• pp.75-90
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• 2010

Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.25-33
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• 1998

Intestinal absorption of ${\beta}-lactam$ antibiotics and angiotensin converting enzyme(ACE) inhibitors has been shown to use the carrier-mediated transport system. In vitro experiments have established that the efficacy of uptake by enterocytes depends on an inwardly directed proton gradient. It was suggested that benazepril was mediated by tripeptide transport system and that amoxicillin was transported by dipeptide transport carrier. The aim of this study is to assess the influence of amoxicillin on the intestinal absorption of benazepril using in vitro diffusion chamber and in situ single pass perfusion technique in the rat in order to elucidate whether the above transport systems are competitive or not. We obtained the gastrointestinal pemeability coefficient of amoxicillin, benazepril and both of them using in vitro diffusion chamber. And also the gastrointestinal absorption clearance of amoxicillin, benazepril and both of them using in situ single-pass perfusion method at steady state were calculated. Amoxicillin and benazepril were analyzed by HPLC. The results by the use of diffusion chamber in vitro indicated that the apparent intestinal permeability coefficient of benazepril was significantly(p<0.01) decreased by amoxicillin(45.2%) and vice versa significantly(p<0.01) decreased(89.1%). The results by the in situ gastrointestinal single-pass perfusion method indicated that the intestinal absorption clearance of benazepril was significantly(p<0.05) decreased by amoxicillin (40.2%) and vice versa significantly(p<0.05) decreased(54.8%). These results might suggest that they share the same peptide carrier pathway for oral absorption.

• 응용통계연구
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• 제28권2호
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• pp.159-174
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• 2015

최근에 Dragomiretskiy와 Zosso (2014)는 경험적모드분해의 단점을 보완하여 새로운 신호 분해방법인 변동모드분해법(Variational Mode Decomposition)을 고안하였다. 기본적으로 변동모드분해법은 경험적모드분해법에 비하여 주파수 탐색 및 분리(tone detection and tone separation)에 탁월한 성능을 보인다. 또한 고속퓨리에변환을 기반으로 한 알고리즘을 사용하여 경험적모드분해법보다 잡음에 강건하다는 장점이 있다. 하지만 변동모드분해법은 결측 등으로 신호가 동일한 시간간격 혹은 공간적 간격으로 측정되지 않은 경우 제대로 동작하지 않는 단점이 있다. 이를 보완하기 위해서 본 논문에서는 변동모드분해법에 다단계우도함수를 조합하는 새로운 방법을 제안한다. 여기에서 다단계우도함수는 변동모드분해법이 신호를 적절한 내재모드함수로 분해하기 전에 결측치를 대체하는 효율적인 방법을 제시한다. 모의실험과 실제 자료의 사례연구를 통하여 변동모드분해법이 기존의 방법보다 더 효율적으로 신호를 분해한다는 것을 보일 것이다.