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Silymarin Modulates Cisplatin-Induced Oxidative Stress and Hepatotoxicity in Rats

  • Mansour, Heba Hosny;Hafez, Hafez Farouk;Fahmy, Nadia Mohamed
    • BMB Reports
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    • v.39 no.6
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    • pp.656-661
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    • 2006
  • Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

Chemical Characteristics and Immuno-stimulating Properties of Biopolymers Extracted from Acanthopanax sessiliflorus

  • Jeong, Sang-Chul;Jeong, Young-Tae;Yang, Byung-Keun;Song, Chi-Hyun
    • BMB Reports
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    • v.39 no.1
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    • pp.84-90
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    • 2006
  • During our search for macrophage stimulating compounds from medicinal plants, we isolated biopolymers from Acanthopanax sessiliflorus. Isolated fraction AS-5 showed maximum potential, and stimulated lysosonal enzymatic activity by 230% at $300\;{\mu}g/ml$. The nitric oxide (NO) producing ability of AS-5 $100\;{\mu}g/ml$ was $58\;{\mu}M$ when treated with interferon-$\gamma$ and lipopolysaccharide $20\;{\mu}g/ml$. The lymphocyte proliferating effects of isolated biopolymer fractions were also investigated. Highest lymphoproliferative activity (a 2.8-fold enhancement compared to saline treated group was exhibited by AS-3 at $200\;{\mu}g/ml$ followed by AS-5 and AS-6. The AS-3 fraction stimulated only T-lymphocytes and had little or no effect on B-lymphocyte proliferation. Partially methylated alditol acetates were prepared to elucidate the glycosyl linkage-compositions of the AS-3 and AS-5 biopolymers, and were analyzed by GC-MS. The AS-3 and AS-5 biopolymer fractions were found to contain 2,3,4-tri-O-methyl-D-glucitol, 2,3,4-tri-O-methyl-D-galacitol 3,4,6-tri-O-methyl-galacitol, 2-O-methyl-arabinitol and 2,4,6-tri-O-methyl-D-glucitol, 2,3,6-tri-O-methyl-D-galacitol linkages, respectively.

Effect of Ginseng on Visceral Nucleic Acid Content of Rats (고려인삼이 흰쥐의 장기조직 핵산 함유량에 미치는 영향)

  • Kim, Chul;Choi, Hyun;Kim, Chung-Chin;Kim, Jong-Kyu;Kim, Myung-Suk;Huh, Man-Kyung
    • The Korean Journal of Physiology
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    • v.5 no.1
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    • pp.23-42
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    • 1971
  • I. Chemical analysis A study was planned to see if administration of ginseng extract has any influence upon the adrenal, the hepatic, the splenic, and the pancreatic nucleic acid contents of rats, and to estimate the effect of ACTH administration as a substitute for stress reaction upon these nucleic acid contents of rats previously primed with ginseng. Ninety male rats$(body\;weight:\;150{\sim}200gm)$ were divided into the ginseng, the saline, and the normal control groups, which received for 5 days 0.5ml/100 gm body weight of ginseng extract solution (4 mg of ginseng alcohol extract in 1 ml of saline), same amount of saline, or no medication, respectively. On the 5th experimental day, each of the 3 groups was further divided into 2 subgroups yielding the ginseng, the ginseng-ACTIT, the saline, the saline-ACTH, the normal control, and the normal-ACTH subgroups. The ginseng, the saline, and the normal control subgroups were sacrificed 3 hours after the last medication, while the ginseng-ACTH, the saline·ACTH, and the normal-ACTH subgroups received ACTH(0.1 unit/subject) 1 hour after the last medication and were sacrificed after 1 more hour. The adrenal gland, the liver, the spleen and the pancreas of each rat were measured for RNA and DNA contents using the chemical method of Schmidt-Thannhauser-Schneider. Following results were obtained: 1. Adrenal RNA and DNA contents and RNA/DNA ratio were all significantly higher in the ginseng group compared with the values obtained from the normal control and the saline groups. Generally administration of ACTH reduced nucleic acid contents of the viscera examined. However, in the ginseng group the rate of decrease [(value of ginseng-ACTH subgroup-value of ginseng subgroup) x100/value of ginseng subgroup)] in adrenal RNA and DNA contents and in RNA/DNA ratio were more conspicuous than they were in the normal control and the saline groups. 2. Hepatic RNA and DNA contents and RNA/DNA ratio were all significantly less in the ginseng group than in the normal control and the saline groups. After ACTH, the rate of decrease in hepatic RNA, DNA, and RNA/DNA ratio of the ginseng· group was less conspicuous than those of the other 2 groups. 3. With regard to the splenic nucleic acid contents, the RNA and the RNA/DNA values of the ginseng group were higher than those of the normal control group but lower than those of the saline group, while the DNA value of the ginseng group was lower than that of the normal control group but higher than that of the saline group. Following administration of ACTH, the rate of decrease in RNA and DNA contents and in RNA/DNA ratio of the ginseng group was more conspicuous than that of the normal control group but less remarkable than that of the saline group. 4. Pancreatic RNA and DNA contents were notably lower in the ginseng group than in the normal control and the saline groups. However, the RNA/DNA ratio of the ginseng group was higher than that of the normal control and the saline groups.'After ACTH, the rate of decrease in pancreatic RNA and RNA/DNA ratio of the ginseng group was less than that of the normal. control group but more than that of the saline group, while the DNA content was actually increased in the ginseng group though it decreased in the normal control and the saline groups. Although the results are not clear enough for an accurate interpretation, they seem to indicate that ginseng exerts notable influence upon the RNA and DNA contents and the RNA/DNA ratio of the viscera stodied. On the whole the drug tends to increase the RNA and DNA contents and RNA/DNA ratio of the adrenal gland but seems to diminish the values of the other 3 viscera. In the early period following ACTH, ginseng facilitates the fall in RNA and DNA contents and RNA/DNA ratio of the adrenal gland, while it tends to reduce the fall in the values of the other viscera studied. II. Autoradiographic and histochemical analysis It was planned autoradiographically and histochemically to affirm and extend the results obtained in part I with regard to the chemically assessed change in the adrenal, the pancreatic, the hepatic and the splenic DNA and RNA contents under the influence of ginseng and ACTH. Fourty male mice (body weight: $18{\sim}20gm$) and 20 male rats were used. Each animal species was divided into the saline, the ginseng, the saline-ACTH, and the ginseng-ACTH groups according to the administered drugs. In the mice, the adrenal, the pancreatic, the splenic and the hepatic DNA-synthetic activity was assessed autoradiographically after administration of $^3H$-thymidine. In the rats, the RNA content of the above 4 organs was assessed histochemically after staining them with methylgreen pyronine. Following results were obtained: 1. Labeled cells were significantly more numerous in the adrenal cortex, the spleen and the liver of the ginseng group than in those of the saline group, although they were less numerous in the pancreas of the ginseng group than in the pancreas of the saline group. The adrenocortical, the pancreatic, the splenic and the hepatic tissues were stained with methylgreen pyronine more deeply in the ginseng group than in the saline group. 2. The adrenocortical, the pancreatic, the splenic and the hepatic tissues contained labeled cells less numerously in the saline-ACTH and the ginseng-ACTH group than in the saline and the ginseng groups. All these tissues were also stained with methylgreen pyronine less deeply in the saline-ACTH and the ginseng-ACTH groups than in the saline and the ginseng groups. 3. However, the adrenal cortex, the spleen, the pancreas, and the liver contained labeled cells more numerously in the ginseng-ACTH group than in the saline-ACTH group. the 4 tissues were stained with methylgreen pyronine more deeply in the ginseng-ACTH group than in the saline-ACTH group. It is inferred from the above results that though with exception, the ginseng mostly facilitates cellular synthesis of nucleic acids and mitigates reduction in nucleic acid content of tissues after administration of ACTH.

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Effect of Water Extract of Korean White and Red Ginseng on Lipolytic Action of Toxohormone-L from Cancerous Ascites Fluid (고려인삼의 수용성 엑기스 성분이 암독소 호르몬-L의 체지방 분해작용에 미치는 영향)

  • 이성동;이광승
    • Journal of Ginseng Research
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    • v.16 no.1
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    • pp.7-12
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    • 1992
  • This study was carried out to investigate the effect of water extracts from 4-, 5- and 6-year old red white ginseng roots on the inhibition of lipolysis in fat cells induced by toxohormone-L which has been known as lipolytic and anorexigenic factors. Toxohormone-L was obtained by partial purification of the ascites fluid from mice which had been inoculated with sarcoma-180. Each water extract of ginseng was effective in vitro against the inhibition of lipolysis induced by the toxohormone-L at the concentrations over 10~100 $\mu\textrm{g}$/ml. At the concentration of 1,000 $\mu\textrm{g}$/ml, the inhibition ratio of lipolysis by the water extracts of 4-, 5- and 6-year old white ginseng roots were 56.3, 59.7 and 59.4%, and those of red ginseng roots were 78.6, 79.1 and 82.5%, respectively, indicating that the 6-year old red ginseng was the most effective in the inhibition of the lipolysis. The total inhibitory activity per gram of ginseng sample was higher in the 4-year and 5-year old white ginseng roots at the concentrations of 100 $\mu\textrm{g}$/ml and 1,000 $\mu\textrm{g}$/ml, respectively, while for the red ginseng it was higher in the 6-year old ginseng than other ages regardless of the reaction concentration. Only once injection of the ginseng extracts(300 mg/ml in saline solution) with 10 ${mu}ell$/g of weight to the mice bearing sarcoma-180 was not effective against the extension of their life spans. On the contrary, the life spans of the mice were rather shortened by the injection of 5-year old white ginseng and 6-year old red ginseng, as compared to that of control.

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Comparison of Heparin Solution and 0.9% Normal Saline Solution Flushing to Secure the Patency of Non-Tunneled Central Venous Catheters (비턴넬형 중심정맥관 개방성 유지를 위한 헤파린 희석액 관류와 생리식염수 관류의 비교)

  • Kim, Ji Hye;Seo, Eun Ji;Park, Hee Jung;Kim, Si Hyeon;Min, Ja;Park, Jeong Yun;Kim, Song Cheol
    • Journal of Korean Clinical Nursing Research
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    • v.20 no.3
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    • pp.326-336
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    • 2014
  • Purpose: The purpose of this study was to compare the effectiveness of heparin and 0.9% normal saline solution flushing for maintaining patency of non­tunneled central venous catheters in patients with surgery. Methods: A randomized controlled clinical trial was performed. Fifty­eight patients were prospectively enrolled and fifty-four patients were completed the study. The heparin group consisted of 30 patients given 100u/ml diluted heparin flushing and the normal saline group consisted of 24 patients with 0.9% sodium chloride flushing. Results: There was no significantly difference in occlusion between the heparin group and the normal saline group in non­tunneled central venous catheters' occlusion. Also there was no difference between these two groups in catheter­related infections. Conclusion: Flushing with 0.9% normal saline is as effective as flushing with heparin solution in maintaining the patency of non­tunneled central venous catheters. In this study, however, the duration of central line use was short and the infection occurrence was little. Further studies are warranted with a larger sample size at multiple centers.

Influence of gineng on the weight of vicera in rats (고려인삼이 흰쥐의 장기 무게에 미치는 영향)

  • Moon, Yung-Been;Park, Won-Ho
    • The Korean Journal of Physiology
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    • v.4 no.2
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    • pp.33-36
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    • 1970
  • A study was planned to see if the ginseng has any influence upon the weight of viscera of male and female rats. One hundred and ten male rats (body weight: $35{\sim}40\;gm$ at the beginning of the experiment) and an equal number of females with similar body weight were use4 Excluding 10 male and 10 females which served as controls, these rats were divided equally into 4 groups (male ginseng group, male saline group, female ginseng group and female saline group), each of which comprising 50 animals. For 45 days, the male and female ginseng groups received every day 0.6 m1/100 gm body weight of ginseng extract solution (4 mg of ginseng alcohol extract in 1 ml of saline) subcutaneously, and the male and female saline groups received the same amount of physiological saline. Each group was further divided into 5 subgroups comprising 10 animals, and the 10 control rats and each subgroups were sacrificed immediately before, and 5, 15, 35, 35, and 45 days after beginning of the drug administration, respectively. The body weight of each subgroup was checked immediately before sacrificing it, and the heart, lung, liver, kidney, adrenal gland, spleen, and testis or uterus of each animal were weighed with a torsion balance. Following results were obtained: 1. Ginseng significantly facilitated gain in weight of testis and spleen as well as body weight of rats from 35th day after beginning of the drug administration on, but not before this time. 2. Ginseng did not exert significant influence upon the weight of heart, lung, liver, tidney, adrenal gland, and uterus of the rat.

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Studies on Ultrastructure of Rat's Liver Cell and Fetal Liver Cell Treated by Actinomycin D (Actinomycin D가 흰쥐의 모체 및 태아 간세포에 미치는 영향에 관한 전자현미경적 연구)

  • Hahn, K.J.;Ko, K.S.;Choi, C.Y.;Choi, C.K.;Choe, R.S.
    • Applied Microscopy
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    • v.13 no.1
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    • pp.71-84
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    • 1983
  • This study was made to investigate the ultrastructural changes of the hepatocyte of the maternal liver, and fetal liver by Actinomycin D in Wistar rats at the stage of pregnancy. Peritoneal injection of Actinomycin D to rats carried out gestation day 7 to 9 at the level of $15{\mu}g(11.5{\mu}g/100g$ body wt.), $20{\mu}g(15.8{\mu}g/100g$ body wt.) on each day. Treated animals with saline only were used for controls. Animals were sacrificed on day 15 of gestation. On electron microscopic examination, the hepatocytes of maternal liver given Actinomycin D $15{\mu}g$/ml had evidence of serious cellular damage, for example, hypertrophy of rough endoplasmic reticulum, loss in nucleolar osmiophilia, swelling of Golgi apparatus and change of mitochondrial structure. Maternal liver given Actinomycin D $20{\mu}g/ml$ shown similar changes to that of the $15{\mu}g/ml$ treated animals. But mitochondria of this group were not changed than that of $15{\mu}g/ml$ treated group. In the hepatocytes of fetal liver, changes were more pronounced. The drug produced alteration in nuclei and cytoplasm. The rough endoplasmic reticulum was swollen and there were ribosomes detachement. In addition, damages of mitochondria, Golgi apparatus were detected.

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Evaluation of the Low Tube Voltage in the Computed Tomography Scan Technique using a Low Concentration Contrast Agent (저농도 조영제를 사용한 CT검사에서 저관전압 기법에 따른 유용성 평가)

  • Jung, Kang-Kyo;Cho, Pyong-Kon
    • Journal of radiological science and technology
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    • v.39 no.1
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    • pp.71-79
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    • 2016
  • The purpose of this study is computed tomography contrast agent at low concentrations and low tube voltage technique to evaluate the usefulness on the phantom image. By varying the degree of mixture by the contrast medium concentration it was inserted in phantom. It was taken by changing the tube voltage and tube current step by step, and to evaluate the dose and the CT value obtained from the phantom image. As a result, low-contrast, low tube voltage(300 mgI/ml, 100 kV) was reduced by an average 21%(CTDIvol; computed tomography dose indexvol) more standard condition(350 mgI/ml, 120 kV). SNR was increased at all depths of the phantom, respectively 1:10 and 1:20(by diluting a contrast agent and normal saline) 12.2(26%) 6.2(17%). CNR was increased at all depths of the phantom, respectively 1:10 and 1:20(by diluting a contrast agent and normal saline) 11.5(32%), 6.3(26%). Research work on the CT scan is necessary in a variety of studies on the low contrast concentration and low tube voltage techniques for dose reduction and reducing of side effects the contrast agent.

Effects of Mahwangbujaseshin-tang (Mahuangfuzixixintang) (麻黃附子細辛湯) on MIA-Induced Osteoarthritis Rats (마황부자세신탕(麻黃附子細辛湯)이 MIA로 유도된 골관절염 유발 Rat에 미치는 영향)

  • Lee, Hyung-Eun;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.2
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    • pp.65-81
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    • 2014
  • Objectives This study was carried out to find out the anti-osteoarthritic effects of Mahwangbujaseshin- tang (Mahuangfuzixixintang ) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injecting MIA ($50{\mu}l$) into the knee joint of rats. Rats were divided into a 3 groups (n=7). The injection did not fit the normal group. A week later, after the injection of MIA, while control group took normal saline 2 ml, the extract of Mahwangbujaseshin-tang (Mahuangfuzixixintang ) (MBST) (200 mg/kg) was injected to treated group. After that, we examined hind paw weight bearing ability, functions of liver and kidney, serum TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, TIMP-1, MMP-9 and hematology. Volume of cartilage was measured by micro CT arthrography. Injury of synovial tissue was measured by H & E, Safranin-O immunofluorescence. Results 1) DPPH and ABTS free radical scavenging activity of MBST was increased according to concentration of MBST and total phenolic contents were in high level. 2) In RAW 264.7 cells, ROS production was significantly decreased in MBST (at 10, $100{\mu}g/ml$) and NO was also decreased but meaningless in MBST (at $100{\mu}g/ml$). 3) In RAW 264.7 cells, IL-6 production was significantly decreased in MBST (at $100{\mu}g/ml$) and TNF-$\alpha$ and IL-$1{\beta}$ production were also decreased but meaningless in MBST (at $100{\mu}g/ml$). 4) In hind legs weight-bearing measurement, level of weight-bearing was increased. 5) Functions of liver and kidney were not affected. 6) TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, MMP-9 and TIMP-1 production were significantly decreased. 7) In hematology, the levels of neutrophils, monocytes were significantly decreased and the levels of white blood cells, lymphocytes were also decreased but meaningless. 8) In micro CT-arthrography, cartilage volume was significantly increased. 9) Histopathologically, injury on cartilage and synovial membrane of MBST group was decreased. Conclusions Based on all results mentioned above, Mahwangbujaseshin-tang (Mahuangfuzixixintang) is believed to be meaningful for suppressing the progress of osteoarthritis. And it is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

The Effect of Increased Dilution Volume and Prolonged Infusion Time of Vancomycin on Incidence of Adverse Reactions through Peripheral Venous Cannulae (말초정맥을 통한 반코마이신희석과 주입시간연장이 부작용발생에 미치는 영향)

  • Oh, Myeong Ju;Kim, Mae Ja
    • Korean Journal of Adult Nursing
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    • v.12 no.2
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    • pp.196-208
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    • 2000
  • The purpose of the study was to explore the effect of 2 hour infusion of vancomycin(1g) in 200ml of isotonic saline every 12 hour on the frequency of "red man syndrome", phlebitis and length of peripheral catheter placement of infected patients, in order to provide safe infusion method for reducing vancomycinin-duced RMS and phlebitis. The subjects of the study consisted of 16 hospitalized patients; 3 oncology and gastro-intestinal patients, 1 neurological patient, 6 thoracic surgical patients and 6 orthopedic patients, who had received vancomycin from July to October in 1999 at S-hospital. The dependent variables were the incidence of RMS, phlebitis and the length of peripheral catheter placement. The incidence of RMS was checked by an inspector at the first night whenever the infusion method of vancomycin was changed. RMS was observed every 15 minutes during an hour for symptoms of RMS such as itching, erythema, chest pain and systolic blood pressure. Incidence of phlebitis was assessed by inspector twice a day from the insertion of peripheral catheter to the removal of the catheter. The data were analyzed by percentage, mean, $X^2$-test, t-test, repeated ANOVA, and logistic regression analysis using the SPSSWIN program. The results are summarized as follows; 1. No significant difference was identified in frequency of RMS between the experimental group and control group. 2. There was no significant difference in the change of systolic blood pressure as the time goes on between the experimental group and control group. 3. The incidence of phlebitis was significantly lower in the experimental group than in the control group. 4. The length of peripheral catheter placement was significantly longer in the experimental group than in the control group. 5. Other drugs administrated with vancomycin didn't influence the occurrence of phlebitis. However, the infusion method of vancomycin influenced the occurrence of phlebitis. The results suggest that 2 hour infusion of vancomycin(1g) in 200ml of isotonic saline every 12 hours may decrease the incidence of phlebitis and increase the length of peripheral catheter placement compared to 1 hour infusion of vancomycin(1g) in 100ml of isotonic saline every 12 hours. However, it does not reduce the incidence of RMS.

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