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Thirteen-week repeated-dose oral toxicity study of KOB03, a polyherbal medicine for allergic rhinitis, in rats (알러지성 비염 한약제제 KOB의 랫드에서의 13주 반복 경구투여에 의한 독성 연구)

  • Kang, Seok Yong;Park, Yeong-Chul;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.15-21
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    • 2013
  • Objectives : To evaluate the safety of KOB, a polyherbal medicine for allergic rhinitis, we conducted a subchronic toxicology study. Methods : Dried extract of KOB(Lot. No. 11003, yield : 41.1%) was prepared from GLP company (Hanpoong Pharm & Food Co., Ltd). KOB was repeatedly administrated orally of male SD rats at daily dose levels of 500 (G2), 1250 (G3) and 5000 (G4) mg/kg/day for 13 weeks. We recorded the clinical signs of toxicity, body weight, food intake/consumption, optometry, urine analysis, organ weights, hematology, and conducted serum biochemical analysis, necropsy, gross and histological changes in target organs of Sprague-Dawley rats, and clinical chemistry analysis. Results : Neither death nor any toxicological signs were obserbed in KOB at all doses of 500, 1250 and 5000 mg/kg/day during the administration period for thirteen-week. Furthermore, there was no difference in body weight and food-take consumption, optometry, necropsy, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of KOB, during at the observation period for thirteen-week. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from repeated-dose administration of KOB in rats during the observation period. Conclusions : Based on these results, the no observable adverse effect level (NOAEL) of KOB was considered to be 5000 mg/kg/day for male rats under these study conditions.

THE GROWTH OF RAT MANDIBLES FOLLOWING MANDIBULAR RETRACTIVE FORCE (백서 하악골 후방견인후의 하악골 성장에 관한 실험적 연구)

  • Kyung, Hee Moon
    • The korean journal of orthodontics
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    • v.19 no.3
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    • pp.15-33
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    • 1989
  • The purpose of this study was to investigate changes of the mandible of a growing rat when they are subjected to a retractive force and those after removal of the retractive force. The experimental animals were Sprague-Dawley male rats of four weeks of age. A mandible was retracted with 50 grams of force on each side in the posterior and superior direction for 8 hours per day. The animals were sacrificed after 1 week, 2-week and 4-week force application, and after 4-week force application-4-week force removal period. The changes of rat mandibular growth following retractive force on the growing rat mandible were observed histologically and biometrically. The findings were as follows ; 1. Histologically, the thickness of the condylar cartilage was slightly reduced in the anterosuperior region with the retractive force. However, in the group of 4-week force application-4-week force removal, there was no significant difference in the thickness of the condylar cartilage. 2. There were no significant histological changes in the articular disk and glenoid fossa through the experimental period. 3. The length and anterior height of the mandible subjected to the retractive force were significantly smaller and greater than those of the control group. 4. There were no significant differences in the mandibular length between 4-week force application - 4-week force removal and the control group. 5. It was concluded that a mandibular retractive force produced inhibitory effects in the growth of the mandible, but that these effects were not sustained during mandibular growth in this experimental model.

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Single and Four-Week Repeated Oral Toxicity Study of CJ-11555 in Sprague-Dawely Rats (CJ-11555의 Sprague-Dawely 랫드를 이용한 단회 및 4주 반복경구투여 독성시험)

  • 김일환;이성학;최재묵;박지은;김덕열;노현정;김택로;이상호;김영훈
    • Toxicological Research
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    • v.20 no.2
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    • pp.143-151
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    • 2004
  • This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

Mild stimulation of stomach 36 acupuncture point by organic nanoscale SP6 patch improves cellular physiologic functional status of different organs

  • Nazeran, Homer;Blake-Greenberg, Sherry;Haltiwanger, Emily
    • CELLMED
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    • v.2 no.1
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    • pp.10.1-10.6
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    • 2012
  • Acupuncture works by stimulating peripheral sensory nerves and their endings causing an increase in cutaneous blood flow and microcirculation, as well as release of neurotransmitters, neuropeptides, and hormones. SP6 Patch is a nanoscale nontransdermal device that mildly stimulates Stomach 36 (zusanli) and other acupuncture points. As stimulation of these points has been indicated to have an effect on hypothalamic function, it is of great research interest to investigate the effect of SP6 Patch on the physiology of organs that are affected by hypothalamic regulation. Bioelectrical tissue impedance data indicative of cellular physiologic organ function, using an Electro Interstitial Scan (EIS) system, were acquired from hypothalamus, pancreas, liver, intestines, kidneys, thyroid and adrenal glands in 10 (1 male, 9 females) volunteers while wearing the SP6 Patch daily for 1 week. EIS testing was performed at baseline with no patch, 30 min after wearing the patch, and after wearing the patch 12 h/day for 1 week. Subjects were instructed to keep well hydrated during the study period. All subjects served as their own control. The hypothesis was: The SP6 Patch worn 12 h/day on the Stomach 36 acupuncture point for 1 week, may significantly improve cellular physiologic functional status of different organs measured by EIS. All tested organs achieved significant improvement in their functional physiologic status after wearing the SP6 Pach 12 h/day for 1 week compared to baseline with an overall average statistical power > 89%. Based upon these results the hypothesis was accepted as true.

THE EFFECTS OF ALOE VERA ON WOUND HEALING OF $CO_2$ LASER-GINGIVECTOMY SITES IN WHITE RATS. (백서에서 $CO_2$ 레이저를 이용한 치은절제술후 Aloe vera가 치유과정에 미치는 영향)

  • Song, Won-Seok;Chai, Jung-Kiu;Cho, Kyoo-Sung;Kim, Chong-Kwan
    • Journal of Periodontal and Implant Science
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    • v.24 no.2
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    • pp.283-302
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    • 1994
  • Gingivectomy has been utilized as a therapeutic method to remove diseased periodontal pocket wall in order to aid in root planing. Although chemical agents and electrosurgery has been used in addition to the conventional method of using surgical blades, difficulties in controling the depth of chemical penetration and effectively regenerating the gingival tissue as well as the slow wound healing has been pointed out as shortcomings of these methods. This study was designed to assess the effect of Aloe vera on wound healing of gingivectomy sites created by $CO_2$ laser on palatal gingiva of maxillary molar region of white rats. Those sites treated by surgical blades were designated as control, by $CO_2$ laser as Experimental group I, by surgical blades in addition to topical application of Aloe vera as Experimental group II, and by $CO_2$ laser and Aloe vera application as Experimental group III. Animals were sacrificed at 2 days, 3 days, 1 week, 2 weeks and 3 weeks postoperatively, and the specimens were histologically analyzed. The results were as follows : 1. Resorption of blood clots were observed in the control at 3rd day, followed by the rest of the experimental groups at 1 week postoperatively. 2. Persistent inflammation was observed up to 1 week in the control and Experimental group II and III, and until the 2nd week in Experimental group I. 3. Granulation tissue was observed up to 1 week in the control, and 2 weeks in the rest of the groups. 4. Epithelization started on the 2nd day. The control showed the most rapid epithelization, and the process was completed by the 2nd week in all groups. 5. Experimental group II and III, which were treated with Aloe vera, showed similar healing patterns to the control and Experimental group I.

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IMMUNOHISTOCHEMICAL STUDY OF TGF-β ON THE HEALING PROCESS IN THE RAT FEMUR BONE DEFECT (백서의 골 결손부 치유시 Transforming Growth Factor-β의 발현에 대한 면역 조직 화학 연구)

  • Bang, Sung-Jun;Kim, Kyung-Wook;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.20 no.2
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    • pp.173-183
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    • 1998
  • $TGF-{\beta}$ is one of growth factors that may be involved in the formation of bone and cartilage. Multiple studies demonstrate that $TGF-{\beta}$ is involved in regulating cell proliferation, differentiation and matrix synthesis, events observed in frature healing. The apperance of $TGF-{\beta}$ in the fracture during healing was evaluated by immunohistologic localization of $TGF-{\beta}$ using antibody. Twenty Sprauge-Dawley strain white male rats, each weiging about 150grams were used and divided two groups. The one group, the $2{\times}2mm$ bony defect was formed in the right femur. The other group, $4{\times}2mm$ bony defect was formed in right femur. Both group were sacrificed at 3day, 1, 2, 3, 4 week and femur were harvested, paraffin sections were stained with H & E, MT stain, immunihistochemical staining with $TGF-{\beta}$ antibody and observed under light microscope. The result were as follows: 1. New bone formation and cartilagenous tissue was seen at 3day. And in the $2{\times}2mm$ bony defect group, $TGF-{\beta}$ stained the cell surounding new bone. 2. The osteoclast and trabecular was seen at 1week. $TGF-{\beta}$ stained the osteoblast and in the $2{\times}2mm$ bony defect group was stained more than $4{\times}2mm$ bony defect group. 3. The lamella bone and trabecule was seen from 3, 4week, and $TGF-{\beta}$ stained almost negative. From the above finding, we could concluded that $TGF-{\beta}$ stained the osteoblast at early stage and 1week, the peak stain was seen from 1week, and then decreased, almost negative stain was seen at 3, 4week.

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Ginsenosides attenuate the 3-nitropropioic acid-induced rat striatal degeneration in an age-dependent manner

  • Kim, Jong-Hoon;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.29 no.2
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    • pp.100-106
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    • 2005
  • The number of reporting the effects on ginseng's physiological, pharmacological, and behavioral effects has been increased every year. Major active components of Panax ginseng, are the ginsenosides, which are mainly triterpenoid dammarane derivatives. 3-Nitropropionic acid (3-NP) is blown to induce cellular energy deficit and oxidative stress related neurotoxicity via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Intraperitoneal injection of 3-NP produces striatal degeneration. Aged animals was more vulnerable to 3-NP than young animal. We used three different ages of 5-, 8-, and 26-week-old rats. 3-NP alone treatment induced striatal lesion and increased lesion volume with age-dependent manner in 5-, 8-, and 26-week-old rats by $30.2{\pm}5.8$, $v$, and $51.3{\pm}8.4mm^3$, respectively. However, pretreatment of GTS (100 mg/kg/day) before 3-NP reduced striatal lesion in 5-,8-, and 26-week-old rats by $3.15{\pm}6.1$, $8.89{\pm}1.9$, and $27.3{\pm}5.6mm^3$, respectively. Pretreatment of GTS also significantly increased survival rate in 5-week-old rats (3-NP alone: GTS +3-NP = $40.4{\pm}6.3$: $72.5{\pm}9.5\%$) than 8-week-old rats (3-NP alone: GTS + 3-NP : $13.5{\pm}5.2\%$ : $45.1{\pm}3.1\%$). In 26-week-old rats, 3-NP alone treated group died on day 18, whereas GTS +3-NP-treated group prolonged lifespan to 30 days. Thus, pretreatment of GTS before administration of 3-NP extended lifespan in all ages. The present results indicate that aged animals are more vulnerable to 3-NP and GTS pretreatment protected 3-NP-induced striatal damage in different ages of animals.

Effects of stress induced by changes of water temperature on the non-specific defense mechanism in cultured olive flounder, Paralichthys olivaceus (수온 변동 자극이 양식 넙치, Paralichthys olivaceus의 비특이적 생체 방어에 미치는 영향)

  • Lee, Deok-Chan;Kim, Do-Hyung;Kim, Su-Mi;Kang, Myong-Seok;Hong, Mi-Ju;Kim, Hyun-Jeong;Park, Soo-Il
    • Journal of fish pathology
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    • v.15 no.2
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    • pp.65-75
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    • 2002
  • This study was performed to know the effects of stress induced by the daily fluctuation of water temperture from 18$^{\circ}C$ to 25$^{\circ}C$ up and down for 30 days on the defence mechanism of olive flounder. Puralichthys olivaceus. To make clear the temperature stress on the defense mechanism of the tested fish. several factors of immune response such as counting of leucocyte appearance in peripheral blood, phagocytic activity in whole blood cells, nitroblue tetrazolium(NBT) reduction, chemiluminescence(CL) response, and lysozyme activity were investigated at 28 days after giving the change of water temperature. The fish was controlled under the none feeding condition during experimental period. Mortality of the tested fish was rapidly increased up to 22% within the first one week of the experimental period without any additional stress factors. The number of neutrophil of peripheral blood in the tested group was significantly higher than the control group at the 2nd week. but the number of lymphocyte was significantly lower than the control group at the 1st and 3rd day of the experimental period. respectively. In the NBT reduction test, the activity of macrophage in the control group fish was the highest on the 7th day while that in the tested group was on the 3rd day. Also. the phagocytosis of tested group against formalin killed cells was retarded compared with the control. CL response of the tested group was significantly lower from 2nd to 5lh day of the experimental period than the control. 'The lysozyme activity of tested group was remained higher during the experimental period than the control. Even though the tested fish showed different results in some non-specific factors of immune respceses between tested and control group fish, olive flounder seems highly adaptable in repealed water temperature change in condition after one week under the given temperature fluctuation range.

Comparison of lymphocyte DNA damage levels and total antioxidant capacity in Korean and American diet

  • Lee, Min Young;Kim, Hyun A;Kang, Myung Hee
    • Nutrition Research and Practice
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    • v.11 no.1
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    • pp.33-42
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    • 2017
  • BACKGROUND/OBJECTIVE: This study aims to measure the in vitro antioxidant capacity of Korean diet (KD) with American diet (AD) as a control group and to examine the ex vivo DNA damage reduction effect on human lymphocytes. MATERIALS/METHODS: The KD applied in this study is the standard one-week meals for Koreans (2,000 kcal/day) suggested by 2010 Dietary Reference Intakes for Koreans. The AD, which is the control group, is a one-week menu (2,000 kcal/day) that consists of foods that Americans would commonly take in according to the National Health and Nutrition Examination Survey. The antioxidant capacity of each menu was measured by means of the total phenolic assay and 3 in vitro antioxidant activity assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, trolox equivalent antioxidant capacity (TEAC), Oxygen radical absorbance capacity ($ORAC_{ROO{\cdot}}$)), while the extent of ex vivo lymphocyte DNA damage was measured by means of the comet assay. RESULTS: When measured by means of TEAC assay, the in vitro antioxidant capacity of the KD of the day was higher than that of the AD (P < 0.05) while there was no significant difference in total phenolic contents and DPPH and ORAC assays. The ex vivo lymphocyte DNA damage protective effect of the KD was significantly higher than that of the AD (P < 0.01). As for the one-week menu combining the menus for 7 days, the total phenolic assay (P < 0.05) and in vitro antioxidant capacity (P < 0.001, DPPH; P < 0.01, TEAC) of the KD menu were significantly higher than those of the AD menu. Likewise, the ex vivo DNA damage reduction rate of the Korean seven-day menu was significantly higher than that of the American menu (P < 0.01). CONCLUSION: This study demonstrates that the high antioxidant capacity and DNA damage protective effect of KD, which consists generally of various plant foods, are higher than those of typical AD.

Effects of Acute Changes in the Energy and Protein Intake Levels over the Short-term on the Maternal Milk Amino Acid Concentrations in Lactating Mares

  • Matsui, A.;Inoue, Y.;Asai, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.6
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    • pp.855-860
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    • 2005
  • This study was designed to test the effects of changes in energy and protein intake levels on the maternal milk amino acid concentrations over the short-term in lactating mares. Three lactating mares were enrolled for the study 7 weeks after parturition. A low-energy and low-protein diet (LEP) was administered during the first week of the study, followed by administration of a high-energy and high-protein diet (HEP), again for a week (day 1 to day 7), and milk was sampled thrice daily at intervals of 8 h during the study period. The mean amino acid concentrations in the maternal milk, except for those of proline, serine and valine, were significantly higher in the HEP feeding period than during the LEP feeding period (p<0.05). The sum of the concentrations of all the amino acids (TAA) in the maternal milk samples during the HEP and LEP feeding periods was 1,644.9${\pm}$26.9 and 1,542.3${\pm}$36.0 mg/100 g, respectively, the difference between the two was not significant. When the ratio of each amino acid concentration to the TAA in the maternal milk was analyzed, there were significant differences between the HEP and LEP feeding periods for all amino acids, except glycine, serine, alanine and histidine. It was found that the concentrations of glutamic acid+glutamine, serine, threonine, arginine and valine were significantly higher (p<0.05) on day 1 than on day 7 during the LEP feeding period, and there were no such differences during the HEP feeding period. In regard to the effects of changes in the energy and protein intake levels in lactating mares, no changes in milk amino acid concentrations were found following administration of HEP for a week, whereas 7 days of administration of LEP was associated with a decrease in the amino acid concentrations.