• Korean Journal of Clinical Pharmacy
• /
• v.26 no.3
• /
• pp.201-206
• /
• 2016

Objective: Direct current cardioversion for atrial fibrillation could be associated with the risk of thromboembolic events. Anticoagulation therapy with warfarin (INR 2.0-3.0) is recommended 3 weeks before and 4 weeks after cardioversion to reduce the risk of thromboembolism. This study evaluated warfarin therapy in pharmacist-managed anticoagulant services (ACS). Methods: This retrospective study was performed in 106 patients with atrial fibrillation from 2012 to 2013. The primary efficacy endpoint was the composite of stroke, transient ischemic attack, myocardial infarction, and cardiovascular death. The primary safety measure was major bleeding. To evaluate the peri-procedural effects of warfarin treatment, we studied whether target INR was maintained, as well as the maintenance period of the therapeutic range. Quality of treatment was measured by time in therapeutic range (TTR) by using the Rosendaal method. Results: There were no thromboembolic events, but TEE examination at time of cardioversion showed a left atrial thrombus in three patients (2.8%). Bleeding complications after cardioversion occurred in 2 patients (1.9%). The average INR value at the time of cardioversion was $2.59{\pm}0.8$, and was within the therapeutic range in 83 patients (78%). Analysis of the patients in whom the value was within the therapeutic range twice consecutively showed that the ratio of TTR was 80% and the therapeutic range was maintained in 67 patients (63%) for an average of 4.90 weeks prior to cardioversion. Similarly, 76 patients (72%) had a stable INR within the therapeutic range for an average of 5.70 weeks and a mean TTR of 83%. Conclusion: Pharmacists significantly contributed to appropriate warfarin treatment with close monitoring during cardioversion. Likewise, active pharmacist monitoring and systemic management should be considered to reduce thromboembolism and bleeding complications in the peri-cardioversion period.

• Progress in Medical Physics
• /
• v.22 no.1
• /
• pp.12-17
• /
• 2011

This study has its own goal to deliver the accurate dose on the target volume by calculating and modifying the attenuation rate of photon beam transmitting the couch top with geometric model. The experiment was that the transmission rate and attenuation rate of photon beam transmitting the couch top was predicted by the geometric model, then compared and analyzed with what was measured experimentally based on that. The result showed that the predicted value by the geometric model accorded closely with the experimental value. In addition, in order to judge whether the practical clinical application is available, the point dose, measured after modifying the attenuation rate modelinged according to the treatment plan of a patient of spine radiosurgery, was compared with the one done nothing. The result was that the former showed decreased error range with treatment planned one than the latter. This papers calculated the transmission and attenuation rate with the geometric model transmitting the couch top and verified it experimentally. This method is expected to be very useful in not only the radiosurgery using Novalis but also the general radiation therapy.

• Korean Journal of Clinical Pharmacy
• /
• v.9 no.1
• /
• pp.27-34
• /
• 1999

The goal of oral anticoagulation therapy with warfarin is to maintain INR values within the therapeutic range in order to prevent complications such as bleeding and thrombosis. The purposes of this study were to investigate the current level of anticoagulation control using INR values, to investigate the incidences of thromboembolism and bleeding complications, and to compare the effect of low intensity INR regimen with therapeutic range recommended by ACCP (American College of Chest Physician). Two hundred three patients with mechanical heart valve replacement done at Yonsei University Cardiovascular Center between January 1994 and December 1996 were selected and reviewed retrospectively. The target INR ranges of $2.5\sim3.5$ (ACCP standard) and low intensity INR of $2.0\sim3.5$ were used for evaluation. According to ACCP standard, $51.2\%$ of patients and $31.1\%$ of INR values were within the therapeutic range when average INR and cumulative INR were used, respectively. Applying low intensity INR values of $2.0\sim3.5$, the therapeutic control was achieved in $57.4\%\;and\;90.1\%$, using average INR and total INR, respectively. The incidences of major and minor bleedings were $0.5\%\;and\;26.6\%$, respectively. The incidence of thromboembolism was $0.5\%$. There was no significant difference in terms of complication incidences between INR $2.0\sim2.5\;and\;INR\;2.5\sim3.5$ groups. However, INR values at the time of bleeding were generally high. In conclusion, the evaluation of patients with mechanical heart valve replacement showed low level of therapeutic control with warfarin therapy. This is partially explained by the fact that the physicians at Yonsei University Cardiovascular Center were using lower intensity INR values as a goal than recommended INR. Also, in the near future, systematic anticoagulation service should be implemented at various hospitals in Korea so that patients on anticoagulant therapy can be more closely monitored to be within the recommended INR by ACCP.

• Radiation Oncology Journal
• /
• v.14 no.2
• /
• pp.149-158
• /
• 1996

Purpose : To get an accute steepness of dose gradients at outside the target volume in intracranial lesion and a less limitation of beam selection avoiding the high dose at normal brain tissue, this Photon Knife Radiosurgery System was developed in order to provide the three-dimensional dose distribution through the reconstruction of CT scan and the combined stereotactic trans-multiarc beam mode based on linear accelerator photon beam. Materials and methods : This stereotactic radiosurgery, Photon Knife based on linear accelerator photon beam was provided the non-coplanar multiarc and trans-multiarc irradiations. The stereotactic trans-multiarc beam mode can be obtained from the patient position in decubitus. This study has provided the 3-dimensional isodose curve and anatomical structures with the surface rendering technique. The dose distribution from the combined two trans-multiarcs (2M 2TM) was compared to that of four non-coplanar multiarcs (4M) with same collimator size of 25 mm in a diameter and total gantry movements. Results : In this study, it shows that the dose distributions of stereotactic beam mode are significantly depended on the selected couch and gantry angle in same collimator size. Practical dose distribution of combined stereotactic trans-multiarc beam has shown a more small rim thickness than that of the non-coplanar multiarc beam mode in axial, sagittal and coronal plane in our study. 3-Dimensional dose line displayed with surface rendering of irregular target shape is helpful to determine the target dose and to predict the prognosis in follow-up radiosurgery. Conclusions : 3-Dimensional dose line displayed with surface rendering of irregular target shape is essential in stereotactic radiosurgery. This combined stereotactic trans-multiarc beam has shown a less limitation of the selection couch and gantry beam angles for the target surrounding critical organs. It has shown that the dose distribution of combined trans-multiarc beam greatly depended on the couch and gantry angles. In our experiments, the absorbed dose has been decreased to $27%$ / mm in maximum at the interval of $50\%$ to $80\%$ of isodose line.

• Korean Journal of Agricultural Science
• /
• v.38 no.1
• /
• pp.109-113
• /
• 2011

The purpose of this study was to examine the potentiality of urban forest roads as an environment for enhancing physical fitness. Six male university students participated in the study as subjects. The subjects walked on an urban forest road for 30 minutes. As a control experiment, they also walked on a national park trail for 30 minutes. Subjects' heart rates were monitored during the walks to calculate the ratio of the average time their heart rates were within the target range (from 60% to 80% of the maximal heart rate) for Enhancing Physical Fitness. After the walks, images of the spaces were analyzed using the semantic differential (SD) method. During the walk on the urban forest road, subjects' heart rates were within the target range 63.3% of the time, and lower than the target range 36.7% of the time. During the control experiment on the national park trail, subjects' heart rates were within the target range only 23.3% of the time, and higher than the target range 76.7% of the time. From the spatial perception evaluation using the SD method, subjects' comfortable and natural feelings when they were on the national park trail were significantly greater than when they were on the urban forest trail, but there were no differences in terms of other SD descriptors, such as friendliness and likeability. The results of our study indicate that the urban forest road provides a good environment for walking to enhance physical fitness. Although not as close to nature as national park trails, urban forest roads offer similar natural environments and have a high potentiality for serving as leisure spaces for urban residents who seek physical activities.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1997.04a
• /
• pp.40-47
• /
• 1997

New quinolones generally have a broad antibacterial spectrum against gram-positive, gram-negative, glucose-nonfermenting and anaerobic bacteria. Some of newly developed quinolones have potent activities against S. aureus including MRSA, S.pneumoniae including PRSP, B. fragilis, chlamydiae, mycoplasmas and mycobacteria as well, and show good activities against various strains resistant to antibacterial agents of other classes. Quinolones display postantibiotic effects in vitro and are bactericidal at concentrations similar to or twice that of the minimum inhibitory concentrations (MICs) for susceptible pathogens. In experimental murine infection models including systemic infections with various pathogens such as S. aureus, S. pyogenes, S. pneumoniae, E. coli and P. aeruginosa, quinolones have shown good oral efficacy as well as parenteral efficacy. Good oral absorption and good tissue penetration of quinolones account for good therapeutic effects in clinical settings. The target of quinolones are two structurally related type II topoisomerases, DNA gyrase and DNA topoisomerase IV. Quinolones are shown to stabilize the ternary quinolone-gyrase-DNA complex and inhibit the religation of the cleaved double-stranded DNA. Bacteria can acquire resistance to quinolones by mutations of these target enzymes. Mutation sites and amino acid changes in DNA gyrase and DNA topoisomerase IV are similar in the organisms examined, suggesting that the mechanism of quinolone resistance in the target enzymes is essentially the same among various organisms. Quinolones act on both the target enzymes to different degrees depending on the organisms or agents tested, and bacteria become highly resistant to quinolones in a step-wise fashion. Incomplete cross-resistance among quinolones in some strains of E. coli and S. aureus suggests the possibility of finding quinolones active against quinolone-resistant strains which are prevailing now. To find such quinolones, the potency toward two target enzymes and the membrane permeability including influx and/or efflux systems should be taken into account.

• Biomolecules & Therapeutics
• /
• v.30 no.1
• /
• pp.48-54
• /
• 2022

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα_i/o and Gα_q/11 heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca²⁺ flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-κB. However, GPR43 shares the same ligands as GPR41, including acetate, propionate, and butyrate, and determination of its precise functions in association with endogenous ligands, such as SCFAs alone, therefore remains a considerable challenge. In this study, we generated novel synthetic agonists that display allosteric modulatory effects on GPR43 and downregulate NF-κB activity. In particular, the potency of compound 187 was significantly superior to that of pre-existing compounds in vitro. However, in the colitis model in vivo, compound 110 induced more potent attenuation of inflammation. These novel allosteric agonists of GPR43 clearly display anti-inflammatory potential, supporting their clinical utility as therapeutic drugs.

• The Journal of Korean Medicine
• /
• v.45 no.1
• /
• pp.114-125
• /
• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• Journal of Life Science
• /
• v.30 no.5
• /
• pp.483-490
• /
• 2020

The ubiquitin system uses ligases and deubiquitinases (DUBs) to regulate ubiquitin position on protein substrates and is involved in many biological processes which determine stability, activity, and interaction of the target substrate. DUBs are classified in six groups according to catalytic domain, namely ubiquitin-specific proteases (USPs); ubiquitin C-terminal hydrolases (UCHs); ovarian tumor proteases (OTUs); Machado Joseph Disease proteases (MJDs); motif interacting with Ub (MIU)-containing novel DUB family (MINDY); and Jab1/MPN/MOV34 metalloenzymes (JAMMs). Otubain 1 (OTUB1) is a DUB in the OTU family which possesses both canonical and non-canonical activity and can regulate multiple cellular signaling pathways. In this review, we describe the function of OTUB1 through regulation of its canonical and non-canonical activities in multiple specifically cancer-associated pathways. The canonical activity of OTUB1 inhibits protein ubiquitination by cleaving Lys48 linkages while its non-canonical activity prevents ubiquitin transfer onto target proteins through binding to E2-conjugating enzymes, resulting in the induction of protein deubiquitination. OTUB1 can therefore canonically and non-canonically promote tumor cell proliferation, invasion, and drug resistance through regulating FOXM1, ERα, KRAS, p53, and mTORC1. Moreover, clinical research has demonstrated that OTUB1 overexpresses with high metastasis in many tumor types including breast, ovarian, esophageal squamous, and glioma. Therefore, OTUB1 has been suggested as a diagnosis marker and potential therapeutic target for oncotherapy.

• Progress in Medical Physics
• /
• v.18 no.2
• /
• pp.93-97
• /
• 2007

This study was designed to evaluate radiosurgery technique using multiple noncoplanar arc therapy with intensity modulated fine MLC shaped photon beam. The stereotactic radiosurgery was performed with 6-MV X-ray beams from a Clinac 21EX LINAC (Varian, Palo Alto, CA, USA) with a MLC-120, which features a full $40{\times}40cm$ field and is the first MLC for general use that offers 0.5 cm resolution for high precision treatment of small and irregular fields. We used a single isocenter and five gantry-couch combinations with a set of intensity modulated arc therapy. We investigated dosimetric characteristics of 2 cm sized spherical target volume with film (X-OMAT V2 film, Kodak Inc, Rochester NY, USA) dosimetry within $25{\times}25cm$ acrylic phantom. A simulated single isocentric treatment using inversely Planned 3D radiotherapy planning system demonstrated the ability to conform the dose distribution to an spherical target volume. The 80% dose level was adequate to encompass the target volume in frontal, sagittal, and transverse planes, and the region between the 40% and 80% isodose lines was $4.0{\sim}4.5mm$ and comparable to the dose distribution of the Boston Arcs. We expect that our radiosurgery technique could be a treatment option for irregular-shaped large intracranial target.