• Animal cells and systems
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• v.10 no.2
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• pp.79-83
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• 2006

Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.168-171
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• 2004

The effects of alterations of dose of xylaznie (X) and Zoltil$\circledR$ (TZ) on canine anesthesia were examined. Experimental groups were divided into three (Group 1: X 1.1 mg/kg and TZ 10 mg/kg, Group 2: X 1.65 mg/kg and TZ 7.5 mg/kg, Group 3: X 2.2 mg/kg and TZ 5 mg/kg), and each had 5 dogs. A femoral artery was catheterized for measurement of blood pressure, and baseline value was measured. The dogs were sedated with xylazine intramuscularly, then after 10 minutes TZ were injected intravenously. Mean arterial blood pressures (MAP), duration of analgesia, mean arousal time (MAT) and mean walking time (MWT) after TZ injection were measured, and the depth of analgesia and the quality of recovery were scored. The values of MAP were recorded from the time of pre-xylazine injection to arousal. Duration of analgesia and was assessed by tail clamping test, and which were done at 10 minutes intervals after TZ injection. The decreases of MAP from 40 minutes after TZ injection were significant (p<0.05). In group 2, MAP at 20 minutes, and from 40 minutes to arousal were significantly decreased (p<0.05). In group 3, MAP were significantly decreased from 40 minutes. MAT were 62.2$\pm$9.2 minutes in group 1, 60.2$\pm$7.5 minutes in group 2, and 71.0$\pm$6.9 minutes in group 3. MAT in group 3 was significantly increased compared with group 2 (p<0.05), and the differences of MWT among each groups were not significant (p>0.05). The scores of quality of recovery were significantly lowered in group 3 compared with group 1 or group 2, which means the side effects of recovery were less occurred. Thus, it was considered that the combination X 2.2 mg/kg IM and TZ 5 mg/kg IV is more effective to surgical procedures and to prevent long and rough recovery of Zoletil anesthesia.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.95-101
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• 2019

Objectives: Angiotensin II (AngII), a major product of renin-angiotensin system (RAS) has important role in induction of hypertension and antihypertensive effect of several medicinal plant was mediated by effect on this agent. Therefore, this study examined the possible effect of hydroalcoholic extract of Crocus sativus (C. sativus) on hypertension induced by AngII. Methods: Six groups (n = 6) of rats were used as follow: 1) Control, 2) AngII (300 ng/kg), 3) Losartan (Los, 10 mg/kg) + AngII and 4-6) C. sativus extract (10, 20 & 40 mg/kg,) + AngII. The femoral artery and vein were cannulated for recording cardiovascular parameters and drugs administration, respectively. All drugs were injected intravenously (i.v). Los and all doses of C. sativus injected 10 min before AngII. Systolic blood pressure (SBP), mean arterial blood pressure (MAP) and heart rate (HR) were recorded throughout the experiment and those peak changes (${\Delta}$) were calculated and compared to control and AngII. Results: AngII significantly increased ${\Delta}MAP$, ${\Delta}SBP$ and ${\Delta}HR$ than control (P < 0. 01 to P < 0.001) and these increments were significantly attenuated by Los. All doses of C. sativus significantly reduced peak ${\Delta}MAP$, ${\Delta}SBP$, and ${\Delta}HR$ than AngII group (P < 0. 05 to P < 0.001). In addition, peak ${\Delta}MAP$, ${\Delta}SBP$ in doses 10 and 20 were significant than Los + AngII group (P<0.05 to P< 0.01) but in dose 40 only MAP was significant (P<0.05). Peak ${\Delta}HR$ in all doses of C sativus was not significant than Los+ AngII. Conclusion: Regarding the improving effect of the C. sativus extract on AngII induced hypertension, it seems that this ameliorating effect partly mediated through inhibition of RAS.

• Progress in Medical Physics
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• v.23 no.1
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• pp.33-41
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• 2012

For applying the quality assurance (QA) of volumetric modulated arc therapy (VMAT) introduced in Eulji Hospital, we classify it into three different QA steps, treatment planning QA, pretreatment delivering QA, and treatment verifying QA. These steps are based on the existing intensity modulated radiation therapy (IMRT) QA that is currently used in our hospital. In each QA step, the evaluated items that are from QA program are configured and documented. In this study, QA program is not only applied to actual patient treatment, but also evaluated to establish a reference of clinical acceptance in pretreatment delivering QA. As a result, the confidence limits (CLs) in the measurements for the high-dose and low-dose regions are similar to the conventional IMRT level, and the clinical acceptance references in our hospital are determined to be 3 to 5% for the high-dose and the low-dose regions, respectively. Due to the characteristics of VMAT, evaluation of the intensity map was carried out using an ArcCheck device that was able to measure the intensity map in all directions, $360^{\circ}$. With a couple of dosimetric devices, the gamma index was evaluated and analyzed. The results were similar to the result of individual intensity maps in IMRT. Mapcheck, which is a 2-dimensional (2D) array device, was used to display the isodose distributions and gave very excellent local CL results. Thus, in our hospital, the acceptance references used in practical clinical application for the intensity maps of $360^{\circ}$ directions and the coronal isodose distributions were determined to be 93% and 95%, respectively. To reduce arbitrary uncertainties and system errors, we had to evaluate the local CLs by using a phantom and to cooperate with multiple organizations to participate in this evaluation. In addition, we had to evaluate the local CLs by dividing them into different sections about the patient treatment points in practical clinics.

• Progress in Medical Physics
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• v.17 no.3
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• pp.173-178
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• 2006

The purpose of this study was to evaluate the radiation dose for clinical PET/CT protocols in clinical environments using Alderson phantom and TLDs. Radiation doses were evaluated for both Philips GEMINI 16 slice PET/CT system and GE DSTe 16 slice PET/CT system. Specific organ doses with $^{137}Cs$ transmission scan, high quality CT scan and topogram in philips GEMINI PET/CT system were measured. Specific organ doses with CT scan for attenuation map, CT scan for diagnosis and topogram in GE DSTe PET/CT system were also measured. The organs were selected based on ICRP60 recommendation. The TLDs used for measurements were selected for within an accuracy of ${\pm}5%$ and calibrated in 10 MV X-ray radiation field. The effective doses for $^{137}Cs$ transmission scan, high qualify scan, and topogram in Philips GEMINI PET/CT system were $0.14{\pm}0.950,\;29.49{\pm}1.508\;and\;0.72{\pm}0.032mSv$ respectively. The effective doses for CT scan to make attenuation map, CT scan to diagnose and topogram in GE DSTe PET/CT system were $20.06{\pm}1.003,\;24.83{\pm}0.805\;and\;0.27{\pm}0.008mSv$ respectively. We evaluated the total effective dose by adding effective dose for PET Image. The total PET/CT doses for Philips GEMINI PET/CT (Topogram+$^{137}Cs$ transmission scan+PET, Topogram+high qualify CT+PET) and GE DSTe PET/CT (Topogram +CT for attenuation map+ PET, Topogram+diagnostic CT+ PET) are $7.65{\pm}0.951,\;37.00{\pm}1.508,\;27.12{\pm}1.003\;and\;31.89{\pm}0.805mSv$ respectively. Further study may be needed to be peformed to find optimal PET/CT acquisition protocols for reducing the patient exposure with good image qualify.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.248-251
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• 2002

The intensity modulated radiation therapy (IMRT) with a multileaf collimator (MLC) requires the conversion of a radiation fluence map into a leaf sequence file that controls the movement of the MLC during radiation treatment of patients. Patient dose verification is clinically one of the most important parts in the treatment delivery of the radiation therapy. The three dimensional (3D) reconstruction of dose distribution delivered to the target helps to verify patient dose and to determine the physical characteristics of beams used in IMRT. A new method is presented for the pretreatment dosimetric verification of two dimensional distributions of photon intensity by means of Beam Intensity Scanner System (BISS) as a radiation detector with a custom-made software for dose calculation of fluorescence signals from scintillator. The scintillator is used to produce fluorescence from the irradiation of 6MV photons on a Varian Clinac 21EX. The BISS reproduces 3D- relative dose distribution from the digitized fluoroscopic signals obtained by digital video camera-based scintillator(DVCS) device in the IMRT. For the intensity modulated beams (IMBs), the calculations of absorbed dose are performed in absolute beam fluence profiles which are used for calculation of the patient dose distribution. The 3D-dose profiles of the IMBs with the BISS were demonstrated by relative measurements of photon beams and shown good agreement with radiographic film. The mechanical and dosimetric properties of the collimating of dynamic and/or step MLC system alter the generated intensity. This is mostly due to leaf transmission, leaf penumbra and geometry of leaves. The variations of output according to the multileaf opening during the irradiation need to be accounted for as well. These phenomena result in a fluence distribution that can be substantially different from the initial and calculative intensity modulation and therefore, should be taken into account by the treatment planning for accurate dose calculations delivered to the target volume in IMRT.

• Progress in Medical Physics
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• v.22 no.4
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• pp.206-215
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• 2011

The purpose of this was to investigate the measurement of fluence dose map for the specific patient quality assurance. The measurement of fluence map was performed using 2D matrixx detector. The absorbed dose was measured by a glass detector, Gafchromic film and ion chamber in Hybrid Optimized VMAT Phantom (HOVP). For 2D Matrixx, the results of comparison were average passing rate $85.22%{\pm}1.7$ (RT_Target), $89.96%{\pm}2.15$ (LT_Target) and $95.14%{\pm}1.18$ (G4). The dose difference was $11.72%{\pm}0.531$, $-11.47%{\pm}0.991$, $7.81%{\pm}0.857$, $-4.14%{\pm}0.761$ at the G1, G2, G3, G4. In HOVP, the results of comparison for film were average passing rate (3%, 3 mm) $93.64%{\pm}3.87$, $90.82%{\pm}0.99$. We were measured an absolute dose in steep gradient area G1, G2, G3, G4 using the glass detector. The difference between the measurement and calculation are 8.3% (G1), -5.4% (G2), 6.1% (G3), 7.2% (G4). The using an Ion-chamber were an average relative dose error $-1.02%{\pm}0.222$ (Rt_target), $0.96%{\pm}0.294$ (Lt_target). Though we need a more study using a transmission detector. However, a measurement of real-time fluence map will be predicting a dose for real-time specific patient quality assurance in volume modulated arc therapy.

• IMMUNE NETWORK
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• v.10 no.5
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• pp.145-152
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• 2010

Background: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). Methods: The anti-inflammatory effects of IFE against nitric oxide (NO), $PGE_2$, TNF-${\alpha}$, and IL-6 release, as well as NF-${\kappa}B$ and MAP kinase activation were evaluated in RAW 264.7 cells. Results: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-${\alpha}$ and IL-6. Furthermore, IFE inhibited the NF-${\kappa}B$ activation induced by LPS, which was associated with the abrogation of $I{\kappa}B-{\alpha}$ degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. Conclusion: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-${\kappa}B$ activation via suppression of $I{\kappa}B{\alpha}$ and MAP kinase phosphorylation in macrophages.

• Molecules and Cells
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• v.38 no.3
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• pp.279-284
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• 2015

Obatoclax, a pan-Bcl2 inhibitor, shows antitumor activities in various solid malignancies. Bcl2-deficient mice have shown the importance of Bcl2 in osteoclasts, as the bone mass of the mice was increased by the induced apoptosis of osteoclasts. Despite the importance of Bcl2, the effects of obatoclax on the proliferation and differentiation of osteoclast precursors have not been studied extensively. Here, we describe the anti-proliferative effects of obatoclax on osteoclast precursors and its negative role on fusion of the cells. Stimulation with low doses of obatoclax significantly suppressed the proliferation of osteoclast precursors in a dose-dependent manner while the apoptosis was markedly increased. Its stimulation was sufficient to block the activation of ERK MAP kinase by RANKL. The same was true when PD98059, an ERK inhibitor, was administered to osteoclast precursors. The activation of JNK1/2 and p38 MAP kinase, necessary for osteoclast differentiation, by RANKL was not affected by obatoclax. Interestingly, whereas the number of TRAP-positive mononuclear cells was increased by both obatoclax and PD98059, fused, multinucleated cells larger than $100{\pm}m$ in diameter containing more than 20 nuclei were completely reduced. Consistently, obatoclax failed to regulate the expression of osteoclast marker genes, including c-Fos, TRAP, RANK and CtsK. Instead, the expression of DC-STAMP and Atp6v0d2, genes that regulate osteoclast fusion, by RANKL was significantly abrogated by both obatoclax and PD98059. Taken together, these results suggest that obatoclax down-regulates the proliferation and fusion of osteoclast precursors through the inhibition of the ERK1/2 MAP kinase pathway.

• Journal of Dental Anesthesia and Pain Medicine
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• v.18 no.3
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• pp.143-149
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• 2018

Background: We evaluated the changes in mean arterial pressure (MAP) and heart rate (HR), and the anesthetic and hemostatic effects, after injection of 2% lidocaine containing various concentrations of epinephrine in rats and mice to determine the appropriate concentration of epinephrine in various anesthetic mixtures. Methods: Rats and mice were randomly allocated to experimental groups: 2% lidocaine without epinephrine (L0), 2% lidocaine with epinephrine 1:200,000 (L200), 1:100,000 (L100), and 1:80,000 (L80). Changes in MAP and HR after administration of the anesthetic mixture were evaluated using a physiological recording system in rats. Onset and duration of local anesthesia was evaluated by pricking the hind paw of mice. A spectrophotometric hemoglobin assay was used to quantify the hemostatic effect. Results: MAP increased in response to epinephrine in a dose-dependent manner; it was significantly higher in the L80 group than in the L0 group at 5 min post-administration. The HR was relatively lower in the L0 group than in the L80 group. The time required for onset of action was < 1 min in all evaluation groups. The duration of action and hemostatic effect of the local anesthetic were significantly better in the L200, L100, and L80 groups than in the L0 group. Conclusion: L200 demonstrated relatively stable MAP and HR values with satisfactory efficacy and hemostatic effect. L200 might be a better local anesthetic for dental patients in terms of anesthetic efficacy and safety.