• Title/Summary/Keyword: Injection Dose

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Gintonin, a Panax ginseng-derived LPA receptor ligand, attenuates kainic acid-induced seizures and neuronal cell death in the hippocampus via anti-inflammatory and anti-oxidant activities

  • Jong Hee Choi;Tae Woo Kwon;Hyo Sung Jo;Yujeong Ha;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.390-399
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    • 2023
  • Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study

  • Heejin Bae;Hyewon Oh;Ga Bin Park;Yong Eun Chung
    • Korean Journal of Radiology
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    • v.25 no.3
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    • pp.257-266
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    • 2024
  • Objective: To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. Materials and Methods: Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Results: Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256-0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr (P > 0.99), Cys C (P = 0.262), and MDA (P = 0.139-0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups (P > 0.05). Conclusion: A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

Decision Algorithm of Natural Algae Coagulant Dose to Control Algae from the Influent of Water Works (정수장 유입조류 전처리를 위한 천연조류제거제(W.H.)의 최적주입농도 결정)

  • Jang, Yeo-Ju;Jung, Jin-Hong;Lim, Hyun-Man;Yoon, Young H.;Ahn, Kwang-Ho;Chang, Hyang-Youn;Kim, Weon-Jae
    • Journal of Korean Society of Environmental Engineers
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    • v.38 no.9
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    • pp.482-496
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    • 2016
  • Algal blooms of cyanobacteria (blue-green Algae) due to the eutrophication of rivers and lakes can cause not only the damage by its biological toxins but also the economic loss in drinking water treatment. The natural algae coagulant, a commercial product known as W.H. containing the algicidal and allelopathic material derived from oak, can control algal problems proactively through the coagulation flotation process. However, because there have been no applications of the process for pre-treatment in drinking water plants, we could find no report on the optimum injection dose of W.H.. In this study, we have conducted several sets of jar-tests while changing W.H. dose and concentration of chl-a for (1) Han-river samples and (2) subcultured cyanobacteria samples, and monitored the removal mechanisms of algae intensively. Based on these jar-test results, two linear equations with variables of chl-a and turbidity have been deduced to predict the optimal W.H. dose after the multiple regression analysis using IBM-SPSS. Also, prototypes of automatic control logic have been suggested to inject the optimal W.H. dose promptly in response to the variation of water quality.

GnRH antagonist multiple dose protocol with oral contraceptive pill pretreatment in poor responders undergoing IVF/ICSI

  • Kim, Chung-Hoon;You, Rae-Mi;Kang, Hyuk-Jae;Ahn, Jun-Woo;Jeon, Il-kyung;Lee, Ji-Won;Kim, Sung-Hoon;Chae, Hee-Dong;Kang, Byung-Moon
    • Clinical and Experimental Reproductive Medicine
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    • v.38 no.4
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    • pp.228-233
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    • 2011
  • Objective: To investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP). Methods: A total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP. Results: There were no differences in patients' characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups. Conclusion: GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.

Single Intramuscular-dose Toxicity of Anti-inflammatory Pharmacopuncture in Rats

  • Jung, Da-Jung;Kim, Sung-Chul;Lee, Hyung-Geol;Choi, Yoo-Min;Sin, Min-Seop;Choi, Seok-Woo;Hong, Seung-Won;Song, Beom-Yong;Kim, Jong-Uk;Yook, Tae-Han
    • Journal of Pharmacopuncture
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    • v.16 no.4
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    • pp.22-29
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    • 2013
  • Objectives: This study was performed to analyze the toxicity of the test substance, anti-inflammatory pharmacopuncture (AIP), when used as a single intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find the lethal dose. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were divided into 4 groups of five 5 female and 5 male animals per group. The rats in the three experimental groups received single intramuscular injections with 0.1-$m{\ell}$, 0.5-$m{\ell}$ and 1.0-$m{\ell}$/animal doses of AIP, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intramuscular injection with a 1.0-$m{\ell}$ dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, histopathological tests showed that AIP had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusions: As a result of single intramuscular-dose tests of the test substance AIP in 4 groups of rats, the lethal dose for both males and females exceeded $1.0m{\ell}$/animal. Therefore, AIP is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.

Radiation Absorbed Dose Calculation Using Planar Images after Ho-166-CHICO Therapy (Ho-166-CHICO 치료 후 평면 영상을 이용한 방사선 흡수선량의 계산)

  • 조철우;박찬희;원재환;왕희정;김영미;박경배;이병기
    • Progress in Medical Physics
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    • v.9 no.3
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    • pp.155-162
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    • 1998
  • Ho-l66 was produced by neutron reaction in a reactor at the Korea Atomic Energy Institute (Taejon, Korea). Ho-l66 emits a high energy beta particles with a maximum energy of 1.85 MeV and small proportion of gamma rays (80 keV). Therefore, the radiation absorbed dose estimation could be based on the in-vivo quantification of the activity in tumors from the gamma camera images. Approximately 1 mCi of Ho-l66 in solution was mixed into the flood phantom and planar scintigraphic images were acquired with and without patient interposed between the phantom and scintillation camera. Transmission factor over an area of interest was calculated from the ratio of counts in selected regions of the two images described above. A dual-head gamma camera(Multispect2, Siemens, Hoffman Estates, IL, USA) equipped with medium energy collimators was utilized for imaging(80 keV${\pm}$10%). Fifty-nine year old female patient with hepatoma was enrolled into the therapeutic protocol after the informed consent obtained. Thirty millicuries(110MBq) of Ho-166-CHICO was injected into the right hepatic arterial branch supplying hepatoma. When the injection was completed, anterior and posterior scintigraphic views of the chest and pelvic regions were obtained for 3 successive days. Regions of interest (ROIs) were drawn over the organs in both the anterior and posterior views. The activity in those ROIs was estimated from geometric mean, calibration factor and transmission factors. Absorbed dose was calculated using the Marinelli formula and Medical Internal Radiation Dose (MIRD) schema. Tumor dose of the patient treated with 1110 MBq(30 mCi) Ho-l66 was calculated to be 179.7 Gy. Dose distribution to normal liver, spleen, lung and bone was 9.1, 10.3, 3.9, 5.0 % of the tumor dose respectively. In conclusion, tumor dose and absorbed dose to surrounding structures were calculated by daily external imaging after the Ho-l66 therapy for hepatoma. In order to limit the thresholding dose to each surrounding organ, absorbed dose calculation provides useful information.

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Hematological Change in Mice Injected with Radiosensitizer and Irradiated with High-dose Radiation (방사선 증감제를 투여한 마우스에 고 에너지 방사선 조사 후 혈액학적 변화에 관한 연구)

  • Ji, Yeon-Sang;Dong, Kyung-Rae;Jung, Myo-Young;Park, Yong-Soon;Dong, Cha-Bun;Ryu, Young-Hwan
    • The Journal of the Korea Contents Association
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    • v.9 no.12
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    • pp.357-363
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    • 2009
  • The current population of elderly is increasing and the with an extended average lifespan, the frequency of cancerous occurrences have also increased, with these increases and the increase in radiotherapy for cancer patients, recognitions of harm and importance have become known. This article was known tumor treatment of patients with hematopoietic disorder by doing a comparative study on the changes in blood cells caused by the acute effects of trace dose to high dose of radiation exposed to mice. According to the sensitizer injection may give rise to harm to the components of peripheral blood. This material needs to be considered when for treating tumor patients and the risks of hematopoietic harm and believe that radiation therapy will be reasonable.

Study on a Single-Dose Toxicity Test of D-Amino Acid Oxidase (DAAO) Extracts Injected into the Tail Vein of Rats

  • Kang, Jungue;Lee, Eun-Yong;Song, Bong-Keun;Lee, Seung-Deok;Yook, Tae-Han;Ahn, Seong-Hun;Son, Il-Hong;Kim, Sungchul
    • Journal of Pharmacopuncture
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    • v.16 no.2
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    • pp.28-32
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    • 2013
  • Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the $LD_{50}$ of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

Genotoxicity of Colloidal $^{32}P$ Chromic Phosphate in the Mouse Bone Marrow Analyzed by Micronuclei Test (생쥐 골수세포 미소핵 검사에 의한 $^{32}P-colloid$의 유전독성에 관한 연구)

  • Kim, Ji-Yeul;Bom, Hee-Seung;Choi, Keun-Hee;Kim, Hee-Kyung;Wui, In-Sun
    • The Korean Journal of Nuclear Medicine
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    • v.26 no.1
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    • pp.127-132
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    • 1992
  • Colloidal $^{32}P$ chromic phosphate is used to prevent hepatic metastasis from colorectal cancer. It is speculated that the intravenous injection of colloidal $^{32}P$ chromic phosphate can cause genotoxicity. To evaluate the genotoxicity of intravenously injected colloidal $^{32}P$ chromic phosphate, authors performed a micronuclei test in mice bone marrow. Mice (ICR strain, $25\sim30g$) were divided to 4 groups: control, group 1 (19.166 KBq/g, usual therapeutic dose in human), group 2 (191.66 KBq/g), and group 3 (1916.6 KBq/g). Five mice of each group were sacrificed at days 1, 2, 3, 5, 7 and 14. Bone marrow were smeared and stained with Wright-Giemsa method. One thousand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs and NCEs were recorded. The frequency of micronuclei in PCE and NCE in the control group was $0.3{\pm}0.06%\;and\;0.45{\pm}0.10%$, respectively. At group 1, frequency of micronuclei is not different from the control. However, frequencies of micronuclei in PCE at groups 2 and 3 were significantly increased from day 1 and persisted to day 14. The frequency of micronuclei in NCE was increased only at group 3. In conclusion, the frequency of micronuclei increases as the dose of colloidal $^{32}P$chromic phosphate increases, while micronuclei was not induced at the usual therapeutic dose. And the frequency of micronuclei persistently elevated for 14 days in the cases of higer doses.

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Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

  • Jang, Han I;Do, Gyeong-Min;Lee, Hye Min;Ok, Hyang Mok;Shin, Jae-Ho;Kwon, Oran
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.272-277
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    • 2014
  • BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS: Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.