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Chiral Separation of the Enantiomers of Metoprolol and Its Metabolites by High Performance Liquid Chromatography

  • Kim, Kyeong-Ho;Shin, Sang-Duk;Lee, Joo-Hyun;Lee, Sang-Cheal;Kang, Jong-Seong;Mar, Woong-chon;Hong, Seon-Pyo;Kim, Hyun-Ju
    • Archives of Pharmacal Research
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    • v.23 no.3
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    • pp.230-236
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    • 2000
  • (1'R, 2R)-, (1'R, 2S)-, (1'S, 2R)- and (1'S, 2S)-$\alpha$-hydroxymetoprolol; (2R)- and (2S)-O-des-methylmetoprolol; and (2R)- and (2S)-metoprolol acid are major metabolites of (2R)-and (2S)-metoprolol, $\beta$-adrenergic antagonist. The focus of most chiral separation methods until now has been on determination of the enantiomeric parent drug. However, it is just as important to be able to follow the metabolism of the enantiomers and their possible chiral metabolites. Therefore, for the study of stereoselective metabolism and pharmacokinetics of metoprolol, the chiral separation of the enantiomers of metoprolol and its metabolites has been investigated using four chiral stationary phases, i.e., Chiralcel OD, Chiral-AGP, Cyclobond I and Sumichiral OA-4900 columns. Metoprolol acid was resolved only by Sumichiral OA-4900. Chiralcel OD provided the highest separation factor and resolution value for metoprolol and O-desmethylmetoprolol and partially resolved the four stereoisomers of $\alpha$-hydroxymetoprolol. Diastereomeric $\alpha$-hydroxymetoprolols were resolved using the coupled column chromatographic system of two chiral stationary phases, Sumichiral OA-4900 column and Chiralcel OD column.

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Inhibition of Arachidonate Release From Rat Peritoneal Macrophage by Biflavonoids

  • Lee, Song-Jin;Son, Kun-Ho;Chang, Hyeun-Wook;Kang, Sam-Sik;Kim, Hyun-Pyo
    • Archives of Pharmacal Research
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    • v.20 no.6
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    • pp.533-538
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    • 1997
  • Biflavonoid is one of unique classes of naturally-occurring bioflavonoid. Previously, certain biflavonoids were found to possess the inhibitory effects on phospholipase $A_2$ activity and lymphocytes $ proliferation^1$ suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several biflavonoids on arachidonic acid release from rat peritoneal macrophages were investigated, because arachidonic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages labeled with $[^{3}H]$arachidonic acid were activated by phorbol 12-myristate 13-acetate(PMA) or calcium ionophore, A23187, radioactivity released in the medium was increased approximately 4.1-7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, biflavonoids (10 uM) such as ochnaflavone, ginkgetin and isoginkgetin, showed inhibition of arachidonate release from macrophages activated by PMA (32.5-40.0% inhibition) or A23187 (21.7-41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apigenin, a monomer of these biflavonoids, did not show the significant inhibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor, showed an inhibitory effect only against PMA-induced arachidonate release (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of biflavonoids in vivo.

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Mistletoe Lectin Induces Apoptosis and Telomerase Inhibition in Human A253 Cancer Cells through Dephosphorylation of Akt

  • Choi, Sang-Hoi;Lyu, Su-Yun;Park, Won-Bong
    • Archives of Pharmacal Research
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    • v.27 no.1
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    • pp.68-76
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    • 2004
  • Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.

Naturally Occurring Biflavonoid, Ochanflavone, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-derived Mast Cells

  • Son Min-Jung;Moon Tae-Chul;Lee Eun-Kyung;Son Kun-Ho;Kim Hyun-Pyo;Kang Sam-Sik;Son Jong-Keun;Lee Seung-Ho;Chang Hyeun-Wook
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.282-286
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    • 2006
  • Ochnaflavone is a medicinal herbal product isolated from Lonicera japonica that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin $D_2(PGD_2)$ generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with $IC_{50}$ values of $0.6{\mu}M$. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the $PGD_2$ product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene $C_4 (LTC_4)$ in a dose dependent manner, with an $IC_{50}$ value of $6.56 {\mu}M$. These results demonstrate that ochnaflavone has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound strongly inhibited degranulation reaction in a dose dependent manner, with an $IC_{50}$ value of $3.01{\mu}M$. Therefore, this compound might provide a basis for novel anti-inflammatory drugs.

Effects of COVID-2019 on plastic surgery emergencies in Korea

  • Yoon, Young Soo;Chung, Chang Ho;Min, Kyung Hee
    • Archives of Craniofacial Surgery
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    • v.22 no.2
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    • pp.99-104
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    • 2021
  • Background: To fight the coronavirus disease 2019 (COVID-19) pandemic, many countries have implemented social distancing and lockdowns. We investigated the changes in the trauma patterns of emergency plastic surgeries in the midst of a pandemic. Methods: A retrospective review of the medical records of all patients treated for emergency plastic surgeries was performed at our hospital in Seoul. We conducted the analysis between March 1 and June 30, 2020, and compared the data obtained with that of the same period in 2019. We also investigated changes in trauma patterns according to the social distancing level from July 2020 to February 2021. Results: There was a total of 800 emergency plastic surgery patients from March to June 2020, which was less than the 981 in the corresponding period in 2019. The proportion of patients aged 7-17 years and ≥ 80 in 2020 showed a significant decrease. In 2020, patients presenting with facial trauma decreased and hand trauma, markedly laceration, increased significantly. In 2020, more injuries happened at home, whereas significantly fewer injuries happened on the streets. In 2020, slipping and sports injury decreased, whereas penetrating injury increased significantly. In the changes observed according to the social distancing level, there were significant differences in age classification, facial open wound, and the mechanism of injury. Conclusion: Social distancing has caused a change in emergency plastic surgeries. To ensure safe and appropriate treatment, strict epidemiologic workup and protective equipment are required.

Clinical outcomes of a low-cost single-channel myoelectric-interface three-dimensional hand prosthesis

  • Ku, Inhoe;Lee, Gordon K.;Park, Chan Yong;Lee, Janghyuk;Jeong, Euicheol
    • Archives of Plastic Surgery
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    • v.46 no.4
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    • pp.303-310
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    • 2019
  • Background Prosthetic hands with a myoelectric interface have recently received interest within the broader category of hand prostheses, but their high cost is a major barrier to use. Modern three-dimensional (3D) printing technology has enabled more widespread development and cost-effectiveness in the field of prostheses. The objective of the present study was to evaluate the clinical impact of a low-cost 3D-printed myoelectric-interface prosthetic hand on patients' daily life. Methods A prospective review of all upper-arm transradial amputation amputees who used 3D-printed myoelectric interface prostheses (Mark V) between January 2016 and August 2017 was conducted. The functional outcomes of prosthesis usage over a 3-month follow-up period were measured using a validated method (Orthotics Prosthetics User Survey-Upper Extremity Functional Status [OPUS-UEFS]). In addition, the correlation between the length of the amputated radius and changes in OPUS-UEFS scores was analyzed. Results Ten patients were included in the study. After use of the 3D-printed myoelectric single electromyography channel prosthesis for 3 months, the average OPUS-UEFS score significantly increased from 45.50 to 60.10. The Spearman correlation coefficient (r) of the correlation between radius length and OPUS-UEFS at the 3rd month of prosthetic use was 0.815. Conclusions This low-cost 3D-printed myoelectric-interface prosthetic hand with a single reliable myoelectrical signal shows the potential to positively impact amputees' quality of life through daily usage. The emergence of a low-cost 3D-printed myoelectric prosthesis could lead to new market trends, with such a device gaining popularity via reduced production costs and increased market demand.

A dual padding method for ischial pressure sore reconstruction with an inferior gluteal artery perforator fasciocutaneous flap and a split inferior gluteus maximus muscle flap

  • Ku, Inhoe;Lee, Gordon K.;Yoon, Saehoon;Jeong, Euicheol
    • Archives of Plastic Surgery
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    • v.46 no.5
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    • pp.455-461
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    • 2019
  • Background Various surgical management methods have been proposed for ischial sore reconstruction, yet it has the highest recurrence rate of all pressure ulcer types. A novel approach combining the advantages of a perforator-based fasciocutaneous flap and a muscle flap is expected to resolve the disadvantages of previously introduced surgical methods. Methods Fifteen patients with ischial pressure ulcers with chronic osteomyelitis or bursitis, who underwent reconstructive procedures with an inferior gluteal artery perforator (IGAP) fasciocutaneous flap and a split inferior gluteus maximus muscle flap from January 2011 to June 2016, were analyzed retrospectively. The split muscle flap was rotated to obliterate the deep ischial defect, managing the osteomyelitis or bursitis, and the IGAP fasciocutaneous flap was rotated or advanced to cover the superficial layer. The patients' age, sex, presence of bursitis or osteomyelitis, surgical details, complications, follow-up period, and ischial sore recurrence were reviewed. Results All ischial pressure ulcers were successfully reconstructed without any flap loss. The mean duration of follow-up was 12.9 months (range, 3-35 months). Of 15 patients, one had a recurrent ulcer 10 months postoperatively, which was repaired by re-advancing the previously elevated fasciocutaneous flap. Conclusions The dual-flap procedure with an IGAP fasciocutaneous flap and split inferior gluteus maximus muscle flap for ischial pressure ulcer reconstruction is a useful method that combines the useful characteristics of perforator and muscle flaps, providing thick dual padding with sufficient vascularization while minimizing donor morbidity and vascular pedicle injury.

Nasal airway function after Le Fort I osteotomy with maxillary impaction: A prospective study using the Nasal Obstruction Symptom Evaluation scale

  • Kim, Hyo Seong;Son, Ji Hwan;Chung, Jee Hyeok;Kim, Kyung Sik;Choi, Joon;Yang, Jeong Yeol
    • Archives of Plastic Surgery
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    • v.48 no.1
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    • pp.61-68
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    • 2021
  • Background This study evaluated changes in nasal airway function following Le Fort I osteotomy with maxillary impaction according to the Nasal Obstruction Symptom Evaluation (NOSE) scale. Methods This cohort study included 13 patients who underwent Le Fort I osteotomy with maxillary impaction. Nasal airway function was evaluated based on the NOSE scale preoperatively and at 3 months postoperatively. The change in the NOSE score was calculated as the preoperative score minus the postoperative score. If the normality assumptions for changes in the NOSE score were not met, a nonparametric test (the Wilcoxon signed-rank test) was used. Differences in NOSE score changes according to patient characteristics and surgical factors were evaluated using the Kruskal-Wallis test and the Mann-Whitney test. Results Patients ranged in age from 18 to 29 years (mean ±standard deviation [SD], 23.00±3.87 years). Three were men and 10 were women. Eleven patients (84%) had an acquired dentofacial deformity with skeletal class III malocclusion. The preoperative NOSE scores ranged from 40 to 90 (mean±SD, 68.92±16.68), and the postoperative NOSE scores ranged from 25 to 80 (53.84±18.83). The cohort as a whole showed significant improvement in nasal airway function following maxillary impaction (P=0.028). Eleven patients (84%) had either improved (n=8) or unchanged (n=3) postoperative NOSE scores. However, nasal airway function deteriorated in two patients. Patient characteristics and surgical factors were not correlated with preoperative or postoperative NOSE scores. Conclusions Nasal airway function as evaluated using the NOSE scale improved after maxillary impaction.

The Allentown Connection-A Tribute for Lew Jae-duk, the "Father of Korean Plastic Surgery"

  • Geoffrey G. Hallock;Joon Pio Hong
    • Archives of Plastic Surgery
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    • v.50 no.3
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    • pp.225-232
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    • 2023
  • In retrospect, the irony of this story began with the first meeting of these co-authors-in of all places, Coimbatore, India, in 2008, at the 12th International Perforator Flap Course. Here the junior author [hereafter "jp"] demonstrated his unparalleled skills in networking, and soon thereafter journeyed some 11,073 km to Allentown, U.S. to peruse the operating room and clinics of the senior author [sic. ggh] in action. Within 2 years jp orchestrated the presentation of the 14th International Perforator Flap Course, so ggh with great anticipation flew only 6,830 miles to reach Seoul, Korea for his first time. But four years more elapsed before ggh returned again to Korea to be a visiting professor, all the while not quite sure why any Korean would want anything from a country doctor who resided in nowheresville Allentown, Pennsylvania. Yet, an extraordinary fact then was to be unveiled, about which ggh was totally ignorant. The pioneer of plastic surgery in Korea, the first Korean to have completed an accredited plastic surgery fellowship, by coincidence had accomplished all this in . . . . . Allentown. The collegial relationship that evolved between these co-authors, who met by chance, indeed had a precedent coincidence! Was this "by chance" alone or predestination? Amazingly, in a way similar, the origin of plastic surgery itself in Korea also had Allentown connections. As a tribute to Lew Jae-duk, this important story must be here told, so let us now retrace his past in Allentown so we can find how the future was to be not so far away.

A study on the management of drawings of Metropolitan Rapid Transit (도시철도 도면 관리에 관한 연구 -서울시 도시철도공사를 중심으로-)

  • Kim, Miyon
    • The Korean Journal of Archival Studies
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    • no.11
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    • pp.181-214
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    • 2005
  • Metropolitan rapid transit system plays an essential role in the public transportation system of any large city, and its managing agency is usually charged with the responsibility of storing and managing the design drawings of the system. The drawings are important and historically valuable documents that must be kept permanently because they contain comprehensive data that is used to manage and maintain the system. However, no study has been performed in Korea on how well agencies are preserving and managing these records. Seoul Metropolitan Rapid Transit Corporation(SMRT) is the managing agency established by the city of Seoul to operate subway lines 5, 6, 7, and 8 more efficiently to serve its citizens. By the Act on Records Management in Public Institutions(ARMPI), SMRT should establish a records center to manage its records. Furthermore, all drawings produced by SMRT and other third party entities should be in compliance with the Act. However, SMRT, as a form of local public corporation, can establish a records center by its own way. Accordingly, the National Archives & Records Service(NARS) has very little control over SMRT. Therefore, the purpose of this study is to research and analyze the present state of storage and management of the drawings of metropolitan rapid transit in SMRT and is to find a desirable method of preservation and management for drawings of metropolitan rapid transit. In the process of the study, it was found that a records center is being considered to manage only general official documents and not to manage the drawings as required by ARMPI. SMRT does not have a records center, and the environment of management on the drawings is very poor. Although there is a plan to develop a new management system for the drawings, it will be non-compliant of ARMPI. What's happening at SMRT does not reflect the state of all other cities' metropolitan rapid transit records management systems, but the state of creation of records center of local public corporation is the almost same state as SMRT. There should be continuous education and many studies conducted in order to manage the drawings of metropolitan rapid transit efficiently by records management system. This study proposes a records center based on both professional records centers and union records centers. Although metropolitan rapid transit is constructed and managed by each local public corporation, the overall characteristics and processes of metropolitan rapid transit projects are similar in nature. In consideration of huge quantity, complexity and specialty of drawings produced and used during construction and operation of metropolitan rapid transit, and overlap of each local public corporation's effort and cost of the storage and management of the drawings, they need to be managed in a professional and united way. As an example of professional records center, there is the National Personnel Records Center(NPRC) in St. Louis, Missouri. NPRC is one of the National Archives and Records Administration's largest operations and a central repository of personnel-related records on former and present federal employees and the military. It provides extensive information to government agencies, military veterans, former federal employees, family members, as well as researchers and historians. As an example of union records center, there is the Chinese Union Dangansil. It was established by several institutions and organizations, so united management of records can be performed and human efforts and facilities can be saved. We should establish a professional and united records center which manages drawings of metropolitan rapid transit and provides service to researchers and the public as well as members of the related institutions. This study can be an impetus to improve interest on management of not only drawings of metropolitan rapid transit but also drawings of various public facilities.