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Initial Risk Assessment of Disodium Disulphite in OECD High Production Volume Chemical Program

  • Sanghwan Song;Park, Yoonho;Park, Hye-Youn;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • v.18 no.1
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    • pp.23-29
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    • 2002
  • Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

Effects of low dietary cation-anion difference induced by ruminal ammonium chloride infusion on performance, serum, and urine metabolites of lactating dairy cows

  • Wang, Kun;Nan, Xuemei;Zhao, Puyi;Liu, Wei;Drackley, James K.;Liu, Shijie;Zhang, Kaizhan;Bu, Dengpan
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.5
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    • pp.677-685
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    • 2018
  • Objective: The objective of the present study was to determine ammonium chloride tolerance of lactating dairy cows, by examining effects of negative dietary cation anion difference (DCAD) induced by ruminal ammonium chloride infusion on performance, serum and urine minerals, serum metabolites and enzymes of lactating dairy cows. Methods: Four primiparous lactating Chinese Holstein cows fitted with ruminal cannulas were infused with increasing amounts (0, 150, 300, or 450 g/d) of ammonium chloride in a crossover design. The DCAD of the base diet was 279 mEq/kg dry matter (DM) using the DCAD formula (Na + K - Cl - S)/kg of DM. Ammonium chloride infusion added the equivalent of 0, 128, 330, and 536 mEq/kg DM of Cl in treatments. According to the different dry matter intakes (DMI), the resulting actual DCAD of the four treatments was 279, 151, -51, and -257 mEq/kg DM, respectively. Results: DMI decreased linearly as DCAD decreased. Yields of milk, 4% fat-corrected milk, energy-corrected milk, milk fat, and milk protein decreased linearly as DCAD decreased. Concentrations of milk protein and milk urea nitrogen increased linearly with decreasing DCAD. Concentration of Cl- in serum increased linearly and concentration of PO43- in serum increased quadratically as DCAD decreased. Urine pH decreased linearly and calculated urine volume increased linearly with decreasing DCAD. Linear increases in daily urinary excretion of $Cl^-$, $Ca^{2+}$, $PO_4{^{3-}}$, urea N, and ammonium were observed as DCAD decreased. Activities of alanine aminotransferase, aspartate aminotransferase, and ${\gamma}-glutamyl$ transferase in serum and urea N concentration in serum increased linearly as DCAD decreased. Conclusion: In conclusion, negative DCAD induced by ruminal ammonium chloride infusion resulted in a metabolic acidosis, had a negative influence on performance, and increased serum enzymes indicating potential liver and kidney damage in lactating dairy cows. Daily ammonium chloride intake by lactating dairy cows should not exceed 300 g, and 150 g/d per cow may be better.

A Case of a 2-year-old Girl with Type I Gaucher Disease Presenting with Growth Retardation and Leg Pain (2세 여아에서 성장 부진과 다리 통증을 동반한 1형 고셔병 증례)

  • Park, Yesul;Hwang, Jae-Yeon;Hwang, Eun Ha;Cheon, Chong Kun;Lee, Beom Hee;Yoo, Han-Wook;Kim, Yoo-Mi
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.2
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    • pp.63-68
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    • 2017
  • Gaucher disease (GD) is caused by the deficiency of glucocerebrosidase. In pediatric patients with GD, especially Type I GD, enzyme replacement therapy (ERT) can reduce the hepatosplenomegaly and improve the hematologic finding and growth velocity. Herein, we report a 2-year-old girl with Type I GD presented with hepatosplenomegaly, bone pain and growth retardation. A 2 year-old-girl was referred to our hospital due to severe hepatosplenomegaly and growth retardation. She suffered from both leg pain and chronic fatigue. Simple x-ray showed widened distal long bones like that of an 'Erlenmeyer flask' which is associated with GD. The laboratory test showed anemia and thrombocytopenia. The enzyme activity was markedly reduced and the direct sequencing of the GBA gene showed the compound heterozygous mutations, p.G46E and p.L444P. As the G46E have been considered as the protective gene against neuronopathic genotype, we could assess the Type I GD in this patient. After one year of ERT, the growth velocity became 11 cm per year. Bone pain and fatigue disappeared. The volume of liver and spleen was reduced from $683cm^3$ and $703cm^3$ to $590cm^3$ and $235cm^3$, respectively. Although GD is an extremely rare disease in Korea, growth retardation and bone pain in children are the important signs which lead to early detection of GD and a simple radiologic finding is helpful to assess the GD at outpatient clinic. We highlight that the early diagnosis and early ERT is important for good growth and outcome for pediatric patients with GD.

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Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer

  • Bae, Sun Hyun;Moon, Seong Kwon;Kim, Yong Ho;Cho, Kwang Hwan;Shin, Eung Jin;Lee, Moon Sung;Ryu, Chang Beom;Ko, Bong Min;Yun, Jina
    • Radiation Oncology Journal
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    • v.33 no.4
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    • pp.320-327
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    • 2015
  • Purpose: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). Materials and Methods: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the ${\alpha}/{\beta}$ value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to $119Gy_{10}$ (median, $55Gy_{10}$). Nineteen lesions were treated with concurrent chemotherapy (CCRT). Results: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, $PTV{\leq}113mL$ and $BED>48Gy_{10}$ were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. Conclusion: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

The Study on Acute.Subacute Toxicity and Anti-cancer Effect of H Herbal-acupuncture (H-약침(藥鍼)의 급성(急性).아급성(亞急性) 독성실험(毒性實驗) 및 항암효과(抗癌效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kim, Tae-Hui;Kwon, Ki-Rok;Lee, Seon-Goo
    • Journal of Pharmacopuncture
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    • v.5 no.2
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    • pp.120-136
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    • 2002
  • Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.

Pharmacokinetics and Tissue Distribution of DWP20367, a Novel Fluoroquinoloce, in Rats and Beagle Dogs (신규 플루오로퀴놀론계 DWP20367의 흰쥐 및 개에서의 체내동태와 조직분포)

  • 조재열;한승희;김병오;남권호;손호정;유영효;정대영
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.284-291
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    • 1997
  • The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

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Gamma Knife Radiosurgery for Metastatic Brain Tumors with Exophytic Hemorrhage

  • Park, Eun Suk;Lee, Eun Jung;Yun, Jung-Ho;Cho, Young Hyun;Kim, Jeong Hoon;Kwon, Do Hoon
    • Journal of Korean Neurosurgical Society
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    • v.61 no.5
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    • pp.592-599
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    • 2018
  • Objective : Metastatic brain tumors (MBTs) often present with intracerebral hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and reduce radiation toxicity, we used a radiosurgical targeting technique that confines the tumor core within the hematoma when performing GKS in patients with such tumors. We reviewed our experience in this endeavor, focusing on local tumor control and treatment-associated morbidities. Methods : From 2007 to 2014, 13 patients with hemorrhagic MBTs were treated via GKS using our targeting technique. The median marginal dose prescribed was 23 Gy (range, 20-25). GKS was performed approximately 2 weeks after tumor bleeding to allow the patient's condition to stabilize. Results : The primary sites of the MBTs included the liver (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary tumor was a melanoma. The mean tumor volume was $4.00cm^3$ (range, 0.74-11.0). The mean overall survival duration after GKS was 12.5 months (range, 3-29), and three patients are still alive at the time of the review. The local tumor control rate was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%). There was one (8%) instance of local recurrence, which occurred 11 months after GKS in the solid portion of the tumor. No GKS-related complications were observed. Conclusion : Our experience shows that GKS performed in conjunction with our targeting technique safely and effectively treats hemorrhagic MBTs. The success of this technique may reflect the presence of scattered metastatic tumor cells in the hematoma that do not proliferate owing to the inadequate microenvironment of the hematoma. We suggest that GKS can be a useful treatment option for patients with hemorrhagic MBTs that are not amenable to surgery.

Effects of probiotic, prebiotic, and synbiotic with and without feed restriction on performance, hematological indices and carcass characteristics of broiler chickens

  • Abdel-Hafeez, Hassan M.;Saleh, Elham S.E.;Tawfeek, Samar S.;Youssef, Ibrahim M.I.;Abdel-Daim, Asmaa S.A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.5
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    • pp.672-682
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    • 2017
  • Objective: This study was conducted to investigate the effects of probiotic, prebiotic and synbiotic with and without feed restriction on broilers performance, blood parameters, carcass characteristics, and feed cost of production from 1 to 56 days of age. Methods: Two hundred and forty unsexed one day-old chicks of Arbor Acres breed were used. Two trials, I and II, were conducted, with 120 birds in both. Each trial was divided into 4 equal groups. The birds in trial I were fed ad libitum throughout the experiment, while the chicks in trial II were fed ad libitum during the first week of age, then subjected to 5 hours/d of feed restriction from the beginning of the second week up to the end of the experiment. In both trials, the birds in group 1 were fed on a control diet while the other groups were given the same control diet supplemented either with a probiotic in group 2, prebiotic in group 3, or synbiotic in group 4. Results: It was found that chicks fed diets supplemented with probiotic, prebiotic and synbiotic (with and without feed restriction) exhibited higher body weight and feed efficiency than chicks fed the control diets. The feed additives in both trials did not affect hemoglobin, serum total protein, albumin, globulin, glucose, and total cholesterol, except the packed cell volume which was increased in the additive treatments with restriction at the end of the experiment. Moreover, the dietary treatments did not influence the carcass yield. However, the relative weights of liver, gizzard and proventriculus, small intestine and bursa of fabricius were found to be increased. The additives decreased the visible fat in the carcass, with more decreasing effect in the additive groups with restriction. The lowest feed cost per kg of weight gain was observed in the birds fed diets supplemented with synbiotic, probiotic and prebiotic. Feed restriction improved the feed conversion ratio, economic return, but decreased the feed intake, serum total cholesterol and visible fat in comparison with non-restricted groups. Conclusion: The biological feed additives could be routinely added to broiler diets, especially when a feed restriction program is followed. Finally, it can be recommended to restrict feed, and add probiotic or synbiotic to increase weight, improve feed conversion rate and reduce feed cost of production.

Digital Tomosynthesis for Patient Alignment System Using Half-fan Mode CBCT Projection Images (Half-fan 모드를 이용한 방사선치료환자 위치교정을 위한 디지털영상 합성영상기술에 관한 예비연구)

  • Park, Justin C.;Park, Sung-Ho;Kim, Jin-Sung;Han, Young-Yih;Ju, Sang-Gyu;Shin, Eun-Hyuk;Shin, Jung-Suk;Park, Hee-Chul;Ahn, Yong-Chan;Song, Willian Y.
    • Progress in Medical Physics
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    • v.21 no.4
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    • pp.360-366
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    • 2010
  • To generate on-board digital tomosynthesis (DTS) for three-dimensionalimage-guided radiation therapy (IGRT) as an alternative to conventional portal imaging or on-board cone-beam computed tomography (CBCT), two clinical cases (liver and bladder) were selected to illustrate the capabilities of on-board DTS for IGRT. DTS images were generated from subsets of CBCT projection data (45, 162 projections) using half-fan mode scanning with a Feldkamp-type reconstruction algorithm. Digital tomosynthesis slices appeared similar to coincident CBCT planes and yielded substantially more anatomic information. Improved bony and soft-tissue visibility in DTS images is likely to improve target localization compared with radiographic verification techniques and might allow for daily localization of a soft-tissue target. Digital tomosynthesis might allow targeting of the treatment volume on the basis of daily localization.

Enhancement of the Early/Precise Diagnosis Based on the Measurement of SUVs in F-18 FDG PET/CT Whole-body Image (F-18 FDG PET/CT 전신 영상에서 SUVs 측정에 기반한 조기/정밀 진단 연구)

  • Park, Jeong-Kyu;Kim, Sung Kyu;Cho, Ihn-Ho;Kong, Eun-Jung;Park, Myeong-Hwan;Cho, Bok-Yeon
    • Progress in Medical Physics
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    • v.24 no.3
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    • pp.176-182
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    • 2013
  • Through this research, we measure the data for several SUVs such as SUVLBM, SUVBW, and SUVBSA using volume of interest in order to enhance the diagnostic level in whole-body image for healthy examinees via F-18 FDG PET/CT. Maximum value, mean value, standard deviation, and threshold value for each SUVs are shown. The measurement of SUVs are carried out with 31 examinees who have taken whole-body examination with F-18 FDG PET/CT from July, 2012 to August, 2012. To secure the preciseness of measurement, we selected 26 healthy examinees as a subject of measurement according to diagnostic view of a nuclear-medical doctor. We see from the measurement of SUVs of PET/CT that the value of SUVBW is hightest and followed by SUVLBM and SUVBSA in turn regardless of the use of contrast media. By comparing the SUVLBM-maximum data for the group used contrast media with those for the group used no contrast media, there found a trend that the measured values increase when the contrast media are used. Among them, liver, aorta, lumbar-5, and Cerebellum exhibit significant difference (p<0.05). We conclude that our data for SUVs would be basic references in overall image interpretation, and hope that the research using VOI would be active.