Purpose : For the research of Boron Neutron Capture Therapy (BNCT), fast neutrons generated from the MC-50 cyclotron with maximum energy of 34.4 MeV in Korea Cancer Center Hospital were moderated by 70 cm paraffin and then the dose characteristics were investigated. Using these results, we hope to establish the protocol about dose measurement of epi-thermal neutron, to make a basis of dose characteristic of epi-thermal neutron emitted from nuclear reactor, and to find feasibility about accelerator-based BNCT. Method and Materials : For measuring the absorbed dose and dose distribution of fast neutron beams, we used Unidos 10005 (PTW, Germany) electrometer and IC-17 (Far West, USA), IC-18, ElC-1 ion chambers manufactured by A-150 plastic and used IC-l7M ion chamber manufactured by magnesium for gamma dose. There chambers were flushed with tissue equivalent gas and argon gas and then the flow rate was S co per minute. Using Monte Carlo N-Particle (MCNP) code, transport program in mixed field with neutron, photon, electron, two dimensional dose and energy fluence distribution was calculated and there results were compared with measured results. Results : The absorbed dose of fast neutron beams was $6.47\times10^{-3}$ cGy per 1 MU at the 4 cm depth of the water phantom, which is assumed to be effective depth for BNCT. The magnitude of gamma contamination intermingled with fast neutron beams was $65.2{\pm}0.9\%$ at the same depth. In the dose distribution according to the depth of water, the neutron dose decreased linearly and the gamma dose decreased exponentially as the depth was deepened. The factor expressed energy level, $D_{20}/D_{10}$, of the total dose was 0.718. Conclusion : Through the direct measurement using the two ion chambers, which is made different wall materials, and computer calculation of isodose distribution using MCNP simulation method, we have found the dose characteristics of low fluence fast neutron beams. If the power supply and the target material, which generate high voltage and current, will be developed and gamma contamination was reduced by lead or bismuth, we think, it may be possible to accelerator-based BNCT.
Park, Jae-Hoon;Kim, Jong-Hwan;Kim, Joo-Il;Kim, Seung-Jo;Seo, Seong-Hoon;Lee, Kyung-Tae
Journal of Pharmaceutical Investigation
/
v.27
no.1
/
pp.11-14
/
1997
This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by ${\beta}-cyclodextrin$ complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 mg/kg and 68 mg/kg of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation$(DS-{\beta}-CD)$] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that $DS-{\beta}-CD$ was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for $DS-{\beta}-CD$, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that $DS-{\beta}-CD$ exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, $DS-{\beta}-CD$ appears to be less gastrolesive than the standard DS formulation.
Examples and experiences of risk management on radiation under prolonged exposure situation are shown. The accident of the Fukushima dai-ichi nuclear power plant after the great east Japan earthquake (11 March, 2011) elevates background level of environmental radiation around the east Japan. For example, ambient dose equivalent rate around Tohkatsu area next to Tokyo located about 200 km-south from the plant, is about 0.1-0.6 micro-Sv $h^{-1}$ mainly due to $^{134}Cs$ and $^{137}Cs$ falling on the ground soil. This level is about double or up to ten times higher than the genuine natural level around the area. International Commission on Radiological Protection (ICRP) recommends how to face the existing exposure situation; that is the prolonged exposure situation. Referring to ICRP's reports and/or related international/domestic documents, we have been discussing and acting to gain public's safety and relief, who have a possibility to be exposed to prolonged lower-dose radiation. Here, we introduce our several experiences on risk management, especially focusing on risk communication, radiation education to public, and stakeholder involvements into making decision in local governments on radiation protection, relating to the accident.
Kim, Minhyung;Jeong, Hyokeun;Park, Sohyun;Rhie, Sandy Jeong
Korean Journal of Clinical Pharmacy
/
v.28
no.1
/
pp.17-23
/
2018
Objective: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. Methods: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. Results: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. Conclusion: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.
This study was conducted to determine the effects of excess vitamin A on alkaline phosphatase (ALP) activity, contents of calcium-binding protein (CaBP), bone gla-protein (BGP) in culture medium and CaBP mRNA expression in chicken osteoblasts in vitro. Osteoblastic cells in the tibia from 1-day-old Arbor Acre broiler chickens were isolated using enzyme digestion. The subconfluenced cells were divided into eight treatments with six replicates in each treatment and cultured in a medium containing either vehicle or different levels of vitamin A (0, 0.2, 0.6, 1.0, 2.0, 5.0, 10.0 and $20.0\;{\mu}g$/ml), and the control received an equivalent volume of ethanol. The incubation lasted 48 h. The results showed that vitamin A down-regulated ALP activity in the culture medium as well as CaBP mRNA expression of osteoblasts in a linear dose-dependent manner (p = 0.124 and p<0.10, respectively), and suppressed the contents of BGP and CaBP in the culture medium in a quadratic dose-dependent manner (p<0.05 and p<0.10, respectively) with increasing addition of vitamin A. The addition of 0-$0.2\;{\mu}g$/ml vitamin A to the culture medium increased ALP activity, BGP and CaBP contents as well as CaBP mRNA expression compared with other groups, but positive effects of vitamin A tended to be suppressed when vitamin A was increased to $1.0\;{\mu}g$/ml, and adverse effects occurred when vitamin A was increased to 10.0-$20.0\;{\mu}g$/ml. These results implied that there was a threshold level of vitamin A inclusion beyond which inhibitory effects occurred, and the mechanism by which overdose of vitamin A reduced bone growth in chickens was probably reduced osteoblastic cell activity, and inhibited expression of CaBP mRNA and CaBP secretion.
Purpose: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. Materials and Methods: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. Results: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ${\leq}90$ Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Conclusion: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
Jung, Myung-Gi;Do, Gyeong-Min;Shin, Jae-Ho;Ham, Young Min;Park, Soo-Yeong;Kwon, Oran
Nutrition Research and Practice
/
v.7
no.6
/
pp.460-465
/
2013
The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.
The objective of present study was to investigate the anti oxidative and hepatoprotective effects of tomato extracts. Total antioxidant capacity and total antioxidant response were 5.5 and $19.8{\mu}g$ Trolox equivalent per mg of tomato extract, respectively. DPPH radical scavenging activity of tomato extracts ($10mg\;ml^{-1}$) was 70% as compared to 100% by pyrogallol solution as a reference. The effect of the tomato extracts on lipid peroxidation was examined using rat liver mitochondria induced by iron/ascorbate. Tomato extracts at the concentration of $0.5mg\;ml^{-1}$ significantly decreased TBARS concentration. Tomato extracts prevented lipid peroxidation in a dose-dependent manner. The effect of the tomato extracts on reactive oxygen species (ROS) generation was examined using cell-free system induced by $H_2O_2/FeSO_4$. Addition of $1mg\;ml^{-1}$ of tomato extracts significantly reduced dichlorofluorescein (DCF) fluorescence. Tomato extracts caused concentration-dependent attenuation of the increase in DCF fluorescence, indicating that tomato extracts significantly prevented ROS generation in vitro. The effect of tomato extracts on cell viability and proliferation was examined using hepatocyte culture. Primary cultures of rat hepatocytes were incubated with 1mM tert-butyl hydroperoxide (t-BHP) for 90 min in the presence or absence of tomato extracts. MTT values by addition of tomato extracts at the concentration of 2, 10, and $20mg\;ml^{-1}$ in the presence of t-BHP were 13, 33 and 48%, respectively, compared to 100% as control. Tomato extracts increased cell viability in a dose-dependent manner. These results demonstrate that tomato extracts suppressed lipid peroxidation and t-BHP-induced hepatotoxicity and scavenged ROS generation. Thus antioxidant and hepatoprotective effects of tomato extracts seem to be due to, at least in part, the prevention from free radicals-induced oxidation, followed by inhibition of lipid peroxidation.
The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg/kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.
In this study, the authors attempted to produce a medical radiation shielding fiber that can be produced at a nanosize scale and that is, unlike lead, harmless to the human body. The performance of the proposed medical radiation shielding fiber was then evaluated. First, diamagnetic bismuth oxide, an element which, among elements that have a high atomic number and density, is harmless to the human body, was selected as the shielding material. Next, 10-100 nm sized nanoparticles in powder form were prepared by ball milling the bismuth oxide ($Bi_2O_3$), the average particle size of which is $1-500{\mu}m$, for approximately 10 minutes. The manufactured bismuth oxide was formed into a colloidal solution, and the radiation shielding fabric was fabricated by curing after coating the solution on one side or both sides of the fabric. The thicknesses of the shielding sheets prepared with bismuth oxide were 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 1.0 mm. An experimental method was used to measure the absorbed dose and irradiation dose by using the lead equivalent test method of X-ray protection goods presented by Korean Industrial Standards; the resultant shielding rate was then calculated. From the results of this study, the X-ray shielding effect of the shielding sheet with 0.1 mm thickness was about 55.37% against 50 keV X-ray, and the X-ray shielding effect in the case of 1.0 mm thickness showed shielding characteristics of about 99.36% against 50 keV X-ray. In conclusion, it is considered that nanosized-bismuth radiation shielding fiber developed in this research will contribute to reducing the effects of primary X-ray and secondary X-ray such as when using a scattering beam at a low level exposure.
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