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A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Kim, Shin-Yoon;Yoon, Young-Ran
    • Molecules and Cells
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    • v.37 no.8
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    • pp.598-604
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    • 2014
  • Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.

Molecular Identification and Chemical Analysis of Aconiti Kusnezoffii Tuber on the Domestic Markets (국내 시장에서 유통되는 초오의 DNA 감별과 화학적 분석)

  • Jang, Hyeri;Joe, Kyeong-Hwa;Song, Kwangho;Lee, Kyoung Jin;Park, Sait Byul;Lee, Chaemin;Ha, In Jin;Lee, Kyungjin;Suh, Youngbae;Kim, Yeong Shik
    • Korean Journal of Pharmacognosy
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    • v.49 no.2
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    • pp.145-154
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    • 2018
  • Aconiti Kusnezoffii Tuber has been traditionally used to treat the symptoms of rheumatoid arthritis and joint pain. The main constituents are diterpenoid alkaloids such as benzoylmesaconine, benzoylaconine, mesaconitine, aconitine, and hypaconitine. In Korea, Aconiti Kusnezoffii Tuber is officially defined as the tubers of Aconitum kusnezoffii Reichb., A. ciliare Decasisne, and A. triphyllum Nakai. On the other hand, only the tuber of A. kusnezoffii is to be used in China. In order to identify the botanical origin of Aconiti Kusnezoffii Tuber circulated in Korea, we analyzed 24 samples of Aconiti Kusnezoffii Tuber obtained from local markets for comparative DNA analysis. The sequence analysis of nrRNA ITS 1 was useful to distinguish Aconitum species and revealed that the roots of A. karakolicum were circulated in Korean markets without discretion. HPLC quantitative analysis showed that aconitine was detected at the highest amount in A. karakolicum. Authentic diterpenoid alkaloids were coinjected for quantification of aconitine-type ingredients. All data were statistically grouped by Principal Component Analysis (PCA). This study suggests that both molecular and chemical analyses should be utilized for the standardization and the quality control for Aconiti Kusnezoffii Tuber.

Effect of Cimetidine and Phenobarbital on Metabolite Kinetics of Omeprazole in Rats

  • Park Eun-Ja;Cho Hea-Young;Lee Yong-Bok
    • Archives of Pharmacal Research
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    • v.28 no.10
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    • pp.1196-1202
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    • 2005
  • Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

Study on Nutrition Intakes of Long-Lived Men and Women Living in Seven Regions in Jellanam-do: Comparisons between Spring and Fall (전라남도 7개 지역에 거주하는 남녀 장수인의 봄과 가을 영양섭취 실태 비교 연구)

  • Chun, Soon-Sil;Jung, Su-Young;Bing, Dong-Joo;Yoon, Eunju
    • Journal of the East Asian Society of Dietary Life
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    • v.24 no.6
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    • pp.723-738
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    • 2014
  • This study examined nutrient intake of long-lived men and women living in Jeollanam-do (Gangjin, Goksung, Gurye, Damyang, Boseong, Suncheon, Jangheung) which is known as representative Korean longevity area. Using the 24 hr recall method, dietary nutrient intake data were collected from 134 subjects (67 for 80~89 years old, 67 for more than 90 years old) in spring and fall 2012. Nutrient for each subject were calculated using CAN-pro. Subjects' daily mean intake levels of macronutrients, vitamins and minerals were higher in fall than in spring. Compared to KDRIs, subjects less than recommend (RNI/AI). East consumed nutrients compared to KDRIs were folate, potassium, calcium, vitamin $B_1$, vitamin $B_2$ and vitamin E. Subjects 232.8~363.1% of recommended intake level for natrium. The nutrient adequacy ratio (NAR) was 0.87 for subjects in their 80s and 0.79 for than 90 years old. The average NAR of all subjects was 0.83. The index of nutritional quality (INQ) exceeded 1 for most nutrients except for Ca (0.87), K (0.77), vitamin $B_1$ (0.84), vitamin $B_2$ (0.70) and folate (0.68). The average INQ was 1.31. This study concluded that even though long-lived men and women living in Jeollanam-do consumed less than RNIs, nutrition consumption quality was relatively fine based on NAR and INQ results.

Effects of Catgut -Embedding Therapy in Patients with Carpal Tunnel Syndrome: a Retrospective Pilot Study

  • You, Kyung-Gon;Kwon, Young-Dal
    • The Journal of Korean Medicine
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    • v.36 no.2
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    • pp.43-49
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    • 2015
  • Objectives: We evaluated the effect of the traditional Korean medical therapy of catgut-embedding therapy in patients with carpal tunnel syndrome (CTS). Methods: Thirteen patients(20 hands) with CTS underwent catgut-embedding therapy once per week for a total of 1-4 sessions. We measured the time to tingling in the fingers on performing Phalen's test. We also had patients use a visual analog scale (VAS) to indicate the severity of tingling. We also asked about the awakening time at night due to pain and tingling. We controlled the treatment as being limited to four sessions. Even if a patient had not been treated for four sessions, we ended the patient's treatment if symptoms resolved. Results: Patients who received catgut-embedding therapy showed significant improvements in the clinical symptoms of CTS. After treatment, in a total of 19 hands, the status of fourteen was changed from positive to negative in Phalen's test and the average of tingling occurrence time in that test was delayed. Among the 20 hands, the VAS in eight hands changed to zero and the average of VAS score decreased. Furthermore, in nine patients, four could sleep well without the use of a splint. Conclusions: Patients undergoing this traditional Korean medical therapy showed alleviation of finger tingling after even a single treatment. We thus concluded that this traditional Korean catgut-embedding therapy, may be effective for treating CTS. However, to confirm the effects of catgut-embedding therapy on CTS, further tests are required, including under the defined, strict conditions of a randomized controlled trial.

Improvement of FK506 Production in the High-Yielding Strain Streptomyces sp. RM7011 by Engineering the Supply of Allylmalonyl-CoA Through a Combination of Genetic and Chemical Approach

  • Mo, SangJoon;Lee, Sung-Kwon;Jin, Ying-Yu;Suh, Joo-Won
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.233-240
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    • 2016
  • FK506, a widely used immunosuppressant, is a 23-membered polyketide macrolide that is produced by several Streptomyces species. FK506 high-yielding strain Streptomyces sp. RM7011 was developed from the discovered Streptomyces sp. KCCM 11116P by random mutagenesis in our previous study. The results of transcript expression analysis showed that the transcription levels of tcsA, B, C, and D were increased in Streptomyces sp. RM7011 by 2.1-, 3.1-, 3.3-, and 4.1-fold, respectively, compared with Streptomyces sp. KCCM 11116P. The overexpression of tcsABCD g enes in Streptomyces sp. RM7011 gave rise to approximately 2.5-fold (238.1 μg/ml) increase in the level of FK506 production compared with that of Streptomyces sp. RM7011. When vinyl pentanoate was added into the culture broth of Streptomyces sp. RM7011, the level of FK506 production was approximately 2.2-fold (207.7 μg/ml) higher than that of the unsupplemented fermentation. Furthermore, supplementing the culture broth of Streptomyces sp. RM7011 expressing tcsABCD genes with vinyl pentanoate resulted in an additional 1.7-fold improvement in the FK506 titer (498.1 μg/ml) compared with that observed under non-supplemented condition. Overall, the level of FK506 production was increased approximately 5.2-fold by engineering the supply of allylmalonyl-CoA in the high-yielding strain Streptomyces sp. RM7011, using a combination of overexpressing tcsABCD genes and adding vinyl pentanoate, as compared with Streptomyces sp. RM7011 (95.3 μg/ml). Moreover, among the three precursors analyzed, pentanoate was the most effective precursor, supporting the highest titer of FK506 in the FK506 high-yielding strain Streptomyces sp. RM7011.

The Correlation between Cross-sectional Area of Lumbar Paraspinal Muscles and Walking Ability in the Patients with Lumbar Spinal Stenosis (척추관 협착증 환자의 보행능력과 요추 주변 근육 단면적의 상관관계 연구)

  • Kim, Min Chul;Seo, Young Hoon;Lee, Sang Min;Kim, Yu Jong;Hong, Je Rak;Yoo, Do Hyun;Kim, Ji Su;Kim, Tae Gyu;Choi, Jae Young;Kim, Tae-Hun
    • Journal of Korean Medicine Rehabilitation
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    • v.26 no.3
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    • pp.109-117
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    • 2016
  • Objectives The purpose of this study was to investigate the correlation between walking ability of lumbar spinal stenosis patients and the cross-sectional area (CSA) of lumbar paraspinal muscles. Methods This study was carried out on 62 lumbar spinal stenosis patients who had limited walking abilities because of neurogenic claudication (NC). All patients received more than 2 weeks of complex treatment at Mokhuri Neck&Back Hospital. CSA of lumbar paraspinal muscles was measured from axial T2-weighted MRI and divided by CSA of adjacent vertebral body to avoid influence of body statues (RCSA-Relative CSA). Pain Free Walking Distance and Numerical Rating Scale (NRS) was measured before and after treatment. Results The Pain Free Walking Distance had significantly increased in patients who had bigger RCSA of psoas muscle (r=0.313, p<0.05). Conclusions The psoas muscle can be a predictive factor for restoring walking ability of lumbar spinal stenosis patients who have limitations walking.

Comparison of Volatile Compounds of Chamaecyparis obtusa Essential Oil and its Application on the Improvement of Atopic Dermatitis (추출방법에 따른 편백 정유의 향기 성분 비교 및 아토피 개선에의 응용)

  • Lim, Geum-Sook;Kim, Ran;Cho, Hoon;Moon, Young-Sook;Choi, Chang-Nam
    • KSBB Journal
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    • v.28 no.2
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    • pp.115-122
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    • 2013
  • Volatile flavor compounds of Chamaecyparis obtuse essential oil were extracted by simultaneous steam distillation extraction (SDE) and supercritical fluid extraction (SFE) and analyzed by GC-MS. A total of 48 and 50 components were identified in essential oil by SDE and SFE, respectively. Monoterpenes, oxygenated monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, and diterpenes in essential oil by SDE were 37.24, 10.9, 9.61, 0.22, and 0.22%, respectively. In the case of SFE, they were 19.1, 23.3, 22.66, 1.31, and 10.57%, respectively. Antioxidant activities were increased with the increase of essential oil up to $80{\mu}L/mL$, irrespective of extraction method. Especially, when the essential oil concentration extracted by SDE was increased from 20 to $80{\mu}L/mL$, the antioxidant activity was increased from 10.5 to 55.1%. However, over $80{\mu}L/mL$ of essential oil, an equilibrium state was maintained. In the case of essential oil extracted by SFE, it was decreased compared to that of SDE. For the improvement of atopic dermatitis, various cosmetics such as an ato-cide soap, ato-cide spray, and ato-cide lotion containing essential oil extracted by SFE were tested. About over 90% was useful for the improvement of atopic dermatitis after 4 weeks of clinical trial targeting 40 female adults. These results demonstrate that ato-cide soap, ato-cide spray, and ato-cide lotion containing essential oil extracted by SFE could be used in functional cosmetics.

Critical Care Medicine (호흡기내과 의사를 위한 Respiratory Review of 2010)

  • Park, Jie-Hae;Chae, Jin-Nyeong;Choi, Won-Il
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.2
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    • pp.75-80
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    • 2010
  • The year of 2009~2010 brought a number of concepts and new ideas were evaluated with promising results. However, some studies that challenged many beliefs. In acute respiratory distress syndrome (ARDS), recent clinical studies took into consideration of pathophysiologic changes of respiratory system compliance. Meta-analysis of positive end-expiratory pressure trials showed survival benefit of high positive end-expiratory pressure in ARDS. Until now, prone positioning did not show survival benefit in patients with ARDS. Extracorporeal membrane oxygenation (ECMO) based management improved survival in patients with severe ARDS. ECMO can be a management option in severe ARDS. Sedation is a standard practice in critically ill patients needing mechanical ventilation. However, Danish group reported less sedation of critically ill patients receiving mechanical ventilation was associated with an increase in days without ventilation. Although this single center study has some limitations, the overall results are promising. Use of maximal sterile barrier precautions (mask, sterile gown, sterile gloves, and large sterile drapes) with chlorhexidine-impregnated dressing reduced central venous catheter related infection. Selective oropharyngeal decontamination (application of topical antibiotics in the oropharynx) reduced the mortality rate of an intensive care unit (ICU) population. Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial reported intensive glucose control increased mortality among adults in the ICU. Some of the results of above papers are promising. However, some ideas may need for more frequent individual assessment and increase the workload of ICU staffs. Before implementation of new practice in ICU, we should take into consideration of individual hospital situation including human and material resources.

Effect of a 5% naproxen patch on reducing pain caused by separators prior to fixed orthodontic treatment

  • Eslamian, Ladan;Rad, Nazila Akbarian;Nobar, Behnam Rahbani;Mortazavi, Seyed Alireza
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.18 no.3
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    • pp.151-159
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    • 2018
  • Background: The pain involved in orthodontic treatments may involve inflammatory processes. This study evaluated the effect of using a naproxen patch for pain reduction in the separating stage of fixed orthodontic treatment. Methods: In this double-blind, randomized, controlled clinical trial of 35 orthodontic patients (age: 14-19 years) who had pain during separator placement, each patient randomly placed naproxen and placebo patches in the first permanent molar region, in opposite quadrants of the same jaw. Patches were replaced every 8 hours until 3 days after separator placement. Patients recorded their pain perception at 2, 6, and 24 hours, and on days 2 (6 PM), 3 (10 AM and 6 PM), and 7 (10 AM and 6 PM), using a visual analog scale. Mean pain scores were compared for the two patches, and effects of sex and age thereon determined. Results: Data from 29 patients (21 girls, eight boys) were analyzed. Mean pain values decreased over time for both patches (P < 0.001). Recorded pain did not differ significantly between the sexes (P = 0.059) or between those aged <16 and those ${\geq}16years$ (P = 0.106). Mean pain recorded with naproxen patches was statistically significantly less than that with placebo patches at all time points (P = 0.004). Conclusion: The naproxen patch was more efficient than the placebo patch for reducing pain at all time points. The highest pain score was recorded at 6 hours, and the least pain was recorded at the $7^{th}$ day after separator placement.