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In vitro and in vivo Antibacterial Activities and Pharmacokinetics of 8-Fluorociprofloxacin and Ciprofloxacin (8-Fluorociprofloxacin과 Ciprofloxacin의 시험관내 및 생체내 항균효과와 약물동태의 비교)

  • 최경업;정용환;김제학
    • YAKHAK HOEJI
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    • v.37 no.3
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    • pp.235-242
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    • 1993
  • 8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

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Medetomidine Sedation and Its Antagonism by Yohimbine in Dogs (개에서 Medetomidine 진정에 대한 Yohimbine의 길항작용)

  • Heo, Keong-Hee;Lee, Jae-Yeon;Choi, Kyeong-Ha;Cho, Jin-Haeng;Park, Chang-Sik;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.27 no.4
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    • pp.343-347
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    • 2010
  • The purpose of this study was to determine the antagonistic effects of yohimbine on sedation induced in dogs with medetomidine. Six mixed breed dogs were repeatedly used at a 2 weeks withdrawal time in this study. The dogs received $40\;{\mu}g/kg$ of medetomidine followed 15 minutes later by 0.2 ml/kg saline solution (group M) or 0.11 mg/kg yohimbine (group MY). All the dogs were examined before and 5, 15, 30, 45, 60, 75, 90, 120 and 150 minutes after the injection of medetomidine, and the induction and recovery times, vital signs, blood biochemistry and anesthetic quality were recorded. There were significant differences in the recovery of anesthesia between the groups. In both groups the heart rate decreased rapidly down to five minutes after the administration of medetomidine. The activity of ALT, AST and the protein concentration did not change significantly in either group and there was no significant difference between them at any time. Response to noise, muscle tone and analgesic score in the MY group at 30 minutes were significantly lower than those of the M group. When recovering from anesthesia, the dogs treated with yohimbine took less time to achieve sternal recumbency and less time to be able to stand and walk. It was concluded that yohimbine reversed effectively medetomidine sedation in dogs.

Study on diuretic activity and electrolytes excretion of methanol extract of Lippia nodiflora (Verbenaceae) in rats

  • D., Ashok Kumar;GP, Senthilkumar;V., Thamil selvan;UK, Mazumder;M., Gupta;SK, Ray
    • Advances in Traditional Medicine
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    • v.8 no.1
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    • pp.39-46
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    • 2008
  • In the Indian traditional medicine, Lippia nodiflora (Verbenaceae) whole plant is claimed to possess powerful diuretic activity. However, the diuretic potential of this plant is not yet investigated. The aim of this study was to evaluate the diuretic potential of methanol extract of Lippia nodiflora (MELN) in rats. Control (0.9% saline solution, 25 ml/kg, b.w) or urea (1 g/kg b.w) or frusemide (5 mg/kg b.w) and different concentrations of MELN (200 and 400 mg/kg b.w) were intraperitoneally administered (n = 6 per each treatment group) to hydrated rats and their urine output was monitored over a period of 5 h and 24 h after drug administration. The diuretic responses with its electrolyte excretion potency of the extract were highly remarkable in comparison with control animals. The extract at doses of 200 and 400 mg/kg shows a significant increase in volume of urine with increase in $Na^{+}$, $Ca^{2+}$ and $Cl^{-}$ excretion accompanied by the excretion of $K^{+}$ in dose dependent manner. This study suggests that the active component(s) in MELN had similar diuretic effect to that of frusemide. These results validate the traditional use of Lippia nodiflora as a diuretic agent.

Effects of Saseuptang Water Extracts on the Renal Function in Rats (사습탕(瀉濕湯) 전탕액(煎湯液)이 백서(白鼠)의 신장기능(腎臟機能)에 미치는 영향(影響))

  • Min, Young-Kie;Yu, Yun-Cho;Lee, Ho-Sub;Ryu, Do-Gon
    • The Journal of Korean Medicine
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    • v.17 no.1 s.31
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    • pp.212-221
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    • 1996
  • The aim of this experiment was to elucidate the effects of Saseuptang water extract on the renal function plasma renin activity and plasma levels of atrial natriuretic peptide and aldosterone in rat The results were as follows; 1. Water balance decreased significantly after the administration of Saseuptang water extract, 0.4 and 0.8ml/kg. 2. Urine volume increased significantly after the administration of Saseuptang water extract, $0.4\;m{\ell}/kg$. 3. Urinary excretion of chloride increased significantly after the administration of Saseupthang water extract, $0.8\;m{\ell}/kg$. 4. Free water clearance increased significantly after the administration of Saseuptang water extract, $0.8\;m{\ell}/kg$. 5. Urinary excretion of creatinine increased significantly after the administration of Saseuptang water extract, $0.8\;m{\ell}/kg$. 6. Plasma levels of atrial natriuretic peptide (ANP) decreased significantly after administration of Saseupthang water extract, $0.8\;m{\ell}/kg$. These results suggest that the changes of urine volume after the administration of Saseuptang water extracts are related to the increments of glomerular filtration rate and free water clearance, and it is suggested that the changes of renal function by which Saseuotang may related to the renin-angiotensin and atrial natriuretic peptide system.

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Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

  • Nugroho, Agung Endro;Hermawan, Adam;Nastiti, Kunti;Suven, Suven;Elisa, Pritha;Hadibarata, Tony;Meiyanto, Edy
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5785-5790
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    • 2012
  • The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

Induction of Ovulation by Hormone Treatment in Ussurian Bullhead Leiocassis ussuriensis

  • Lim, Sang Gu;Kim, Young Soo;Han, Hyung Kyun;Kim, Kwang Suk;Kim, Dae Jung;Kang, Eon Jong;Son, Sang Gyu;Kim, Eung Oh
    • Development and Reproduction
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    • v.16 no.4
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    • pp.271-277
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    • 2012
  • The effects of ovulation induction in ussurian bullhead, Leiocassis ussuriensis, were investigated by treating ussurian bullhead with hCG, LHRHa, GnRHa, ovaprim, and pimozide. hCG was injected to ussurian bullhead at 0.75% NaCl, 5,000, 10,000, 20,000, and 30,000 IU, respectively. The ovulation inducement rates were 100% in 20,000 and 30,000 IU. Fertilization rates were 82.7% and 79.8%. Hatching rates were 59.4% and 57.2%. Ovulation time was between 16-19 hr The concentrations of LHRHa injected were 0.75 NaCl, 50, 100, 200, 300, and $300{\mu}g/kg$. The ovulation inducement rates were 100% in 300 and $400{\mu}g/kg$. Fertilization and hatching rates were 84.9% and 68.4% at $200{\mu}g/kg$. The times to ovulation were between 23 hr and 34 hr. Ovaprim of 0.75% NaCl, 1.0, 1.5, 2.0, 2.5 and 3.0 ml/kg were injected to the abdominal cavity. The ovulation inducement rate was highest at 2.0 and 3.0 ml/kg to 92% and ovulation time was between 27-38 hr. LHRHa concentrations of 0.75% NaCl, 50, 100, 200, 300 and $400{\mu}g$ were injected with pimozide ($1,000{\mu}g$). Ovulation inducement rate was 100% from 200 to 400 IU with pimozide. Ovulation time was 22-36 h. Fertilization and hatching rates were 88.9% and 70.4% in $200{\mu}g/kg$ with pimozide.

Axenic Culture of Gyrodinium impudicum Strain KG03, a Marine Red-tide Microalga that Produces Exopolysaccharide

  • Yim Joung Han;Lee Hong Kum
    • Journal of Microbiology
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    • v.42 no.4
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    • pp.305-314
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    • 2004
  • An exopolysaccharide-producing microalgal dinoflagellate was isolated from a red-tide bloom and des­ignated strain KG03. A bacteria-free culture of strain KG03 was achieved using a modified wash with phototaxis and antibiotic treatment. Combined treatment with neomycin and cephalosporin was the most effective for eliminating the bacteria associated with the microalgae. Strain KG03 was identified as Gyrodinium impudicum by analyzing the ITS regions of the 5.8S rDNA, 18S rDNA, morphological phenotype and fatty acid composition. The exopolysaccharide production and cell growth in a 300-ml photobioreactor were increased 2.7- and 2.4-fold, respectively, compared with that in a flask culture at the first isolation step.

Effects of Thyroid Hormone on Left Ventricular Volume and Function in Hyperthyroidism (갑상선기능항진증(甲狀線機能亢進症)에서 좌심실용적(左心室容積) 및 기능변화(機能變化)에 관한 연구(硏究))

  • Lee, Myung-Chul;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.17 no.2
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    • pp.1-17
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    • 1983
  • The purpose of this study is to investigate the effects of thyroid hormone on the left ventricular(LV) volume arid function in man with untreated hyperthyroidism and to determine the effects of successful therapy for thyrotoxicosis on the ventricular pathophysiology. In the present study, equilibrium radionuclide cardiac angiography was performed and LV volume index, ejection phase indexes of LV performance, serum thyroid hormone levels and other hemodynamic parameters were measured in 28 normal subjects and 39 patients with hyperthyroidism before treatment and again every 4 weeks for the first 2 months after the initiation of effective therapy. The results obtained were as follows; 1) In the untreated hyperthyroid state heart rate, blood volume, cardiac index and stroke volume index($97{\pm}14$ beats/min, $73.5{\pm}11.8ml/kg,\;6.9{\pm}1.4\;l/min/m^2$ and $77.6{\pm}13.8ml/m^2$, respectively) were increased significantly compared to those in normal control($74{\pm}12beats/min$, $66.6{\pm}14.8ml/kg,\;3.8{\pm}1.2\;l/min/m^2$ and $56.6{\pm}13.2ml/m^2$ respectively). $(Mean{\pm}SD)$ 2) There was a significant increase in LV end-diastolic volume index in patients with hyperthyroidism ($30.5{\pm}7.5$ for hyperthyroid group compared to a normal control of $22.2{\pm}6.5$; p<0.001), whereas end-systolic volume index remained unchanged $9.6{\pm}3.6\;and\;8.8{\pm}3.3$ respectively).3) In patients with hyperthyroidism, LV ejection fraction was $70.0{\pm}5.6%$, fractional shortening $32.9{\pm}5.1%$, mean velocity of circumferential fiber shortening(mean Vcf) $1.34{\pm}0.31$ circ/sec and maximum ejection rate $3.47{\pm}0.80$. All the ejection phase indexes were significantly greater than those in normal control($65.2{\pm}5.7%,\;28.8{\pm}3.2%,\;0.88{\pm}0.37$ circ/see and $2.27{\pm}0.50$, respectively; p<0.001). 4) Effective therapy produced significant decrease in all the values of serum thyroid hormone concentrations(p<0.00l), hemodynamic parameters(p<0.001), end-diastolic volume index(p<0.01) and ejection phase indexes of LV contractility in patients with hyperthyroidism and after one to two months, when the patients were euthyroid, these measurements were in the range of normal. 5) A significant linear correlation between mean Vcf and serum thyroxine level(r=0.63, p<0.001) as well as between mean Vcf and serum triiodothyronine level(r=0.62, p<0.001) was found. The lesser degree of correlation was also noted between other ejection phase indexes and serum thyroid hormone concentrations. The results indicate that the major effects of excess thyroid hormone on the LV in human beings with hyperthyroidism are an enhancement of LV function and an increase in LV enddiastolic volume and that these effects cause predictable reversible cardiac alteration which are changed dramatically and immediately after effective therapy.

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Studies on the Reproductive and Developmental Toxicity of Herbal Medicine Containing Aristolochic Acids

  • Sohn, K-H;Rhee, G-S;Kim, S-S;Kim, S-H;Kwack, S-J;Chae, S-Y;Park, C-H;Kim, B-H;Kil, K-S;Choi, K-S;Park, K-L
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.110-110
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    • 2002
  • Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including chinese herbs. Aristolochic acid, suspected as the causal factor of this renal disease, is a well known carcinogen. It has been known that Madouling (Aristolochiae fructus) contains aristolochic acid. The objective of this study was to investigate the effects of Madouling, Madouling-tang, which are the extract mixture from 10 different chinese herbs including Madouling, and aristolochic acid on reproductive and developmental toxicity. Female rats were administered orally with the extracts of Madouling, madouling-tang, and aristolochic acid from 14 days before mating to day 17 of gestation. Madouling (8mg/kg) decreased fertility in the 8mg/kg group, but Madouling-tang and aristolochic acids did not. Significant decrease of mean fetal body weights were observed in the 16mg/kg group of aristolochic acids. External, visceral and skeletal malformation of fetuses were not observed with treatment. Histopathological examination showed the discrete damage of kidney in the 8mg/kg group of Madouling and 16mg/kg groups of aristolochic acid. In whole embryo culture, Madouling and Madouling-tang caused the retardation of growth and development of embryo in the dose of 1 $\mu$g/ml and 0.02 $\mu\textrm{g}$/kg, respectively while aristolochic acids showed the similar effect in the dose of 300 $\mu\textrm{g}$/kg. These results indicate that Madouling, up to 0.05mg/kg (prescription dose to human) has no adverse effects on the fertility, reproduction and development of Sprague-Dawley rats.

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Age-related Changes in Plasma Leptin from Early Growing to Late Finishing Stages of Castrated Holstein Steers: Utilizing Multi-species Leptin RIA

  • Vega, R.A.;Lee, H.G.;Kuwayama, H.;Matsunaga, N.;Hidari, H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.5
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    • pp.725-731
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    • 2002
  • This experiment was performed to understand the changes in plasma leptin in association with plasma IGF-1, body weight and ADG from early growing to late finishing stages of Holstein steers. Blood collection was performed by arterial vein puncture at selected monthly ages of 1 (54 kg), 2.6 (103 kg), 7.2 (205 kg), 13.5 (314 kg), 16.9 (414 kg), 22.2 (550 kg), 24.9 (626 kg) and 27.4 months (695 kg). The blood was analyzed for leptin using the multi-species leptin RIA with recombinant bovine leptin (rbleptin) as standard, plasma IGF-1 was also measured using RIA. Against the standard rbleptin, the multi-species Leptin RIA system's sensitivity, cross reactivity, slope and recovery of 41.0 ng/ml rbleptin in plasma were 4.9 ng/ml, 11.22%, -1.396 and 97.8%, respectively. Plasma leptin measured were more than 5.0 ng/ml, which enable multi-species RIA system to investigate plasma leptin in normal growing steers. Body weight resulted to a highly significant second-degree polynomial relationship with plasma leptin (q=0.54, p<0.0001) and plasma IGF-1 (q=0.44, p<0.0001) from 1 to 27.4 monthly ages. However, the second-degree polynomial curve of plasma leptin and IGF-1 differs showing a concave and convex curvilinear relationship, respectively. ADG was not significantly associated to plasma leptin (r=0.06, p>0.05) and plasma IGF=1 (r=0.06, p>0.05) from 1 to 27.4 monthly ages. Low coefficient, but significant associated increase of plasma leptin and IGF-1 (r=0.12, p<0.008) from 1 to 27.4 months was observed. The uncoordinated increases of plasma IGF-1 at growing and plasma leptin at fattening period, may indicate (1) indirect involvement of endogenous IGF-1 on leptin secretion, and (2) IGF-1 level may signify lean and bone accretion while plasma leptin may mirror body fatness across the monthly ages of Holstein steers.