• 제목/요약/키워드: Dose-rate effects

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Comparing the Efficacy and Safety on Intravenous Administration of Aminoglycosides Twice versus Thrice Daily (아미노글리코사이드계 항생제의 투약간격에 따른 안전성 및 효과)

  • Lee, Ju Eun;Kim, Ho Soon;Shin, Wan Gyoon;Cho, Nam Chun
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.83-88
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    • 1998
  • Improved knowledge of the time course of antimicrobial activity should provide useful information for designing optimal dosage regimen. In contrast to $\beta$-lactam, aminoglycosides tend to induce a prolonged postantibiotic effect against aerobic or facultative gram negative rods and clinical outcome was significantly correlated with achieving peak serum concentrations. The objective of this study was to compare the efficacy, safety of e same total daily dose of amikacin and gentamicin given either twice or thrice daily in the treatment of patients. Consecutive patients over 20 years old with a suspected or confirmed infection for which an aminoglycosides was indicated were eligible. Exclusion criteria were known allergy to aminoglycosides, renal impairment, granulocytopenia and pregnancy. Patients were treated with intravenous amikacin 15 mg/kg/day or gentamicin 4.5 mg/kg/day either in two devided or in three devided. Seventy-four patients with infection were enrolled in this study of amikacin twice daily (A2, n=29), gentamicin twice daily (G2, n=8) vs amikacin thrice daily (A3, n=30), gentamicin thrice daily (G3, n=7). Baseline characteristics were comparable in G2 and G3. The clinical cure rate (including partial improve) were $89.0\%\;and\;86.0\%$ in A2 group and A3 group respectively. The bacteriologic cure rate were $99.0\%\;and\;85.7\%$ in A2 group and in A3 group respectively. The clinical and bacteriologic effects were difficult to compare G2 with G3, because of the small numbers of patients. The serum creatinin rose in $3.44\%$ (1 in 29) of patients in the A2 group compared to $13.3\%$ (4 in 30) in e A3 group. Although audiometry was not performed, there was no clinical evidence of ototoxicity in any of the patients. In our opinion, twice-daily regimen of aminoglycosides is more effective and less nephrotoxic than thrice-daily regimen.

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Cardiovascular Safety Pharmacology of Sibutramine

  • Yun, Jaesuk;Chung, Eunyong;Choi, Ki Hwan;Cho, Dae Hyun;Song, Yun Jeong;Han, Kyoung Moon;Cha, Hey Jin;Shin, Ji Soon;Seong, Won-Keun;Kim, Young-Hoon;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.386-389
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    • 2015
  • Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

Effect of UV-C irradiation for bacterial disinfection of drinking water (UV-C 조사에 의한 음용수 살균 시스템의 미생물 저해 효과)

  • Kim, Hyun-Joong;Kim, Yun-Jae;Seo, Se-Yeong;Lee, Chang Joo
    • Korean Journal of Food Science and Technology
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    • v.53 no.2
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    • pp.218-222
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    • 2021
  • This study aimed to investigate bacterial disinfection in drinking water using a water purifier. Water artificially inoculated with Escherichia coli and Listeria monocytogenes at various concentrations was irradiated using ultraviolet (UV)-C at a rate of 3.4 L/min in a water purifier, and the disinfection effects of UV-C were evaluated. Both E. coli and L. monocytogenes were disinfected up to 107 colony-forming units (CFU)/2.8 L by the UV-C irradiation. Additionally, morphological study using fluorescence microscopy in conjunction with live/dead staining revealed that both the bacteria species were disinfected by the UV-C irradiation. Therefore, UV-C in water purifiers can effectively kill high concentrations of bacteria in distilled water. UV irradiation (UV-C: 254 nm wavelength, irradiation dose: 40 mJ/㎠) at a flow rate of 3.4 L/min on drinking water has the potential to sterilize bacteria-contaminated drinking water, at least for 3.2×107 CFU/2.8 L of E. coli and 8.4×107 CFU/2.8 L of L. monocytogenes.

Expression of Heat Shock Protein 70 Gene and Body Color Changes in Non-biting Midge Larvae (Glyptotendipes tokunagai) Effected by O3 Treatment (오존(O3) 노출에 의한 조각깔따구(Glyptotendipes tokunagai)의 체색 변화 및 heat shock protein 70 발현 변화)

  • Kim, Won-Seok;Choi, Bohyung;Kim, Moon-Kyung;Chae, Seon Ha;Kwak, Ihn-Sil
    • Korean Journal of Ecology and Environment
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    • v.53 no.4
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    • pp.324-330
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    • 2020
  • Ozone (O3) is a general disinfectant to remove micro-pollutants in water treatment system. Previous studies have reported effect of ozone to bacteria and pathogens removal, but its effect to the relatively large organisms has little known. In this study, we investigated potential effects of ozone toxicity to the non-bite midge larvae (Glyptotendipes tokunagai) with accumulate mortality, coloration change and expression of heat shock protein 70 (HSP70). The accumulate mortality rate of G. tokunagai increased in a dose-time dependent manner and the highest mortality rate was observed to 75% at 30 minute of exposure duration with 2.0 ppm of ozone concentration. Exposure to ozone was a factor increasing body color of the larvae. The tendency of HSP70 mRNA expression showed up-regulation in ozone exposure at 20 minute. After that time, the expression of HSP70 in exposed group decreased to a similar level of control group. Our results clearly showed that ozone toxicity affects physical and molecular activity of G. tokunagai, implying the potential hazardous of ozone in the aquatic ecosystem including macroinvertebrates.

EFFECTS OF $INTERFERON-\gamma$ ON COLLAGEN AND FIBRONECTIN SYNTHESIS IN PRIMARY CULTURED PERIODONTAL LIGAMENT CELLS ($Interferon-\gamma$가 치주인대 세포의 Collagen 및 Fibronectin의 합성과 Alkaline Phosphatase 활성에 미치는 영향)

  • Kim, Gwang-Seok;Sung, Jae-Hyun;Choi, Je-Yong;Ryou, Hyun-Mo
    • The korean journal of orthodontics
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    • v.23 no.2 s.41
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    • pp.229-248
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    • 1993
  • [ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.

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The Effects of Rotational Correlation Time of Paramagnetic Contrast Agents on Relaxation Enhancement: Partial Binding to Macromolecules (거대분자에 부분적으로 결합한 상자성 자기공명 조영제의 회전속도가 이완증강에 미치는 영향)

  • 장용민
    • Investigative Magnetic Resonance Imaging
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    • v.3 no.2
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    • pp.159-166
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    • 1999
  • Purpose : To evaluate the effect of rotational correlation time (${\tau}_R$) and the possible related changes of other parameters, ${\tau}_M,{\;}{\tau}_S,{\;}and{\;}(\tau}_V$ of gadolinium (Gd) chelate on T1 relaxation enhancement in two pool model. Materials and Methods : The NMRD (Nuclear Magnetic Relaxation Dispersion) profiles were simulated from 0.02 MHz to 800 MHz proton Larmor frequency for different values of rotational correlation times based on Solomon-Bloembergen equation for inner-sphere relaxation enhancement. To include both unbound pool (pool A) and bound pool (pool B), the relaxivity was divided by contribution from unbound pool and bound pool. The rotational correlation time for pool A was fixed at the value of 0.1 ns, which is a typical value for low molecular weight complexes such as Gd-DTPA in solution and ${\tau}_R$ for pool B was changed from 0.1 ns to 20 ns to allow the slower rotation by binding to macromolecule. The fractional factor of was also adjusted from 0 to 1.0 to simulate different binding ratios to macromolecule. Since the binding of Gd-chelate to macromolecule cab alter the electronic environment of Gd ion and also the degree of bulk water access to hydration site of Gd-chelate, the effects of these parameters were also included. Results : The result shows that low field profiles, ranged from 0.02 to 40 MHz, and dominated by contribution from bound pool, which is bound to macromolecule regardless of binding ratios. In addition, as more Gd-chelate bound to macromolecule, sharp increase of relaxivity at higher field occurs. The NMRD profiles for different values of ${\tau}_S$ show the enormous increase of low field profile whereas relaxivity at high field is not affected by ${\tau}_S$. On the other hand, the change in ${\tau}$V does not affect low field profile but strongly in fluences on both inflection fie이 and the maximum relaxivity value. The results shows a fluences on both inflection field and the maximum relaxivity value. The results shows a parabolic dependence of relaxivity on ${\tau}_M$. Conclusion : Binding of Gd-chelate to a macromolecule causes slower rotational tumbling of Gd-chelate and would result in relaxation enhancement, especially in clinical imaging field. However, binding to macromolecule can change water enchange rate (${\tau}_M$) and electronic relaxation ($T_le$) vis structural deformation of electron environment and the access of bulk water to hydration site of metal-chelate. The clinical utilities of Gd-chelate bound to macromolecule are the less dose requirement, the tissue specificity, and the better perfusion and intravascular agents.

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Simultaneous Analysis of Bangpungtongseong-san and Its Antioxidant Effect (방풍통성산의 동시분석 및 항산화 효능 연구)

  • Seo, Chang-Seob;Kim, Ohn Soon;Shin, Hyeun-Kyoo
    • Herbal Formula Science
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    • v.21 no.2
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    • pp.133-143
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    • 2013
  • Objectives : We carry out the simultaneous quantification for quality control of four components in Bangpungtongseong-san (BPTSS) sample. In addition, we assessed the antioxidant effects of BPTSS sample. Methods : The used column for separation and analysis of four compounds was Luna C18 column and column oven temperature was maintained at $40^{\circ}C$. The mobile phase for simultaneous determination consisted of two solvent systems, 1.0% acetic acid in water and 1.0% acetic acid in acetonitrile. High performance liquid chromatography-photodiode array (HPLC-PDA) method for analysis was performed at a flow rate of 1.0 mL/min with PDA detection at 254 and 280 nm. The injection volume was 10 ${\mu}L$. The antioxidant activities of BPTSS were evaluated by measuring free radical scavenging activities on 2,2'-Azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) and 1-1-diphenyl-2-picrylhydrazyl (DPPH). The inhibitory effects on low-density lipoprotein (LDL) oxidation were evaluated by the formation of thiobarbituric acid relative substances (TBARS) and relative electrophoretic mobility (REM). Results : Calibration curves were acquired with $r^2{\geq}0.9999$. The values of limit of detection (LOD) and quantification (LOQ) were 0.06-0.29 ${\mu}g/mL$ and 0.20-0.98 ${\mu}g/mL$, respectively. The amounts of geniposide, liquiritin, baicalin, and glycyrrhizin in BPTSS were 5.06, 7.33, 27.56, and 7.81 mg/g, respectively. The BPTSS showed the radical scavenging activity in a dose-dependent manner. The concentration required for 50% reduction (RC50) against ABTS and DPPH radicals were 72.51 ${\mu}g/mL$ and 128.49 ${\mu}g/mL$. Furthermore, GMGHT reduced the oxidation properties of LDL induced by CuSO4. Conclusions : The established HPLC-PDA method will be helpful to improve quality control of BPTSS. In addition, BPTSS has potentials as therapeutic agent on anti-atherosclerosis.

Glycididazole Sodium Combined with Radiochemotherapy for Locally Advanced Nasopharyngeal Carcinoma

  • Li, Ming-Yi;Liu, Jin-Quan;Chen, Dong-Ping;Qi, Bin;Liang, Yu-Ying;Yin, Wen-Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2641-2646
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    • 2014
  • Background: To evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with chemotherapy (cisplatin plus 5-FU/folic acid, PLF) and radiotherapy in treating patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: Patients with III~IV stage nasopharyngeal carcinoma (NPC),were randomly divided into treatment group (46 patients) and control group (45 patients). Both groups received radiotherapy concomitant with PLF chemotherapy. The treatment group at the same time cwas given CMNa ($800mg/m^2$ before radiotherapy), by l h intravenous drip, three times a week. Results: When the dose of radiation was over 60 Gy, complete response rates of nasopharyngeal tumor and lymph node metastases in treatment group were significantly higher than in the control group (93.5% vs 77.8%; 89.1% vs 93.5%, p<0.05). Three months after radiotherapy, complete response rate of nasopharynx cancer and lymph node metastases in treatment group was both 97.8%, again higher than in the control group (84.4% and 82.2%) (p<0.05). In the treatment group, 1, 3, 5 year disease-free survival rates were 95.7%, 86.7% and 54.5%; and in control group, the corresponding disease-free survival rates were 93.3%, 66.2% and 38.6%, respectively, the difference being statistically significant (log-rank =5.887, p=0.015). One, 3, 5 year overall survival rates in two groups of patients were 97.8%, 93.5%, 70.4% and 95.5%, 88.07%, 48.4%, respectively, again with a statistically significant difference (log-rank=6.470, p=0.011). Acute toxicity and long-term radiotherapy related toxicity in the two groups did not differ (p>0.05). Conclusions: Glycididazole sodium could improve curative effects without increasing adverse reactions when treating paitents with locally advanced nasopharyngeal carcinoma.

Effects of Ethanol Extracts from Petasites japonicus S. et Z. Max. on Hepatic Antioxidative Systems in Alcohol Treated Rats (머위 추출물이 알코올 투여한 흰쥐의 간조직 내 항산화 체계에 미치는 영향)

  • Cho, Bae-Sick;Lee, Jae-Joon;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.3
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    • pp.298-300
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    • 2007
  • This study investigated the hepatoprotective effects of an ethanol extract of Petasites japonicus S. et. Z. Max. (PJ) on alcohol-induced liver-damaged rats. Sprague-Dawley rats weighing $100{\sim}150\;g$ were divided into 5 groups; normal diet group (NOR), alcohol (35%, 10 mL/kg/day) treated group (CON), PJ 200 mg/kg/day treated group (PJ1), PJ 200 mg/kg/day and alcohol treated group (PJ2), and PJ 400 mg/kg/day and alcohol treated group (PJ3). The growth rate of the control group was higher than that of normal group, whereas the group administered PJ concomitantly was significantly increased. Also, feed efficiency ratio decreased by alcohol administration was gradually increased to the adjacent level of the normal group by administering PJ. The AST activity in serum elevated by alcohol was significantly decreased by administering the high dosage of PJ, but exerted no significant change on serum ALT activity. It was also observed that the hepatic activities of catalase and GSH-Px increased by alcohol were markedly decreased in PJ2 and PJ3, but not in the activities of XO and SOD as compared with the control group. The depleted content of GSH by alcohol was increased to the level of normal group by administering PJ in a dose-dependant manner. In conclusion, these results suggest that PJ may have a possible protective effect on liver function in hepatotoxicity-induced rat by alcohol administration.

Anti-inflammatory Effects of an Ethanolic Extract form Betula Platyphylla (화피(樺皮)의 항염(抗炎) 효과(效果)에 관(關)한 연구(硏究))

  • Ryu Mi-Hyun;Park Eun-Kyung;Kim Young-Hoon;Lee Yeon-Ah;Lee Sang-Hoon;Yang Hyung-In;Hong Seung-Jae;Baek Yong-Hyeon;Park Dong-Suk;Han Jung-Soo;Yoo Myung-Chul;Kim Kyoung-Soo
    • The Journal of Korean Medicine
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    • v.27 no.1 s.65
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    • pp.184-195
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    • 2006
  • Objectives : Betula Platyphylla(BP) is a traditional analgesic, anti-fungal, anti-inflammatory herb used in Chinese 1medicine. However, no information is available to explain its action. In this study. we investigated the anti-inflammatory 1effects of BP to elutidate the molecular pharmacological activity in the ethanol extract of BP(BPE). Methods : We performed WTS assay in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages with BPE. Nitrite was measured by Griess assay, prostaglandin E2 (PGE2) by enzyme-linked immunosorbent assay (ELISA) in LPS induced RAW264.7 macrophages with BPE. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were determined by Western blot. Activation of nuclear factor-kappaB (NF-kB) was measured by electrophoretic mobility shift assay (EMSA). Results : BPE significantly suppressed production of nitric oxide (NO) and PGE2 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. The maximal inhibition rate of NO and PGE2 production by BPE was ca. 88.8% and 93% at the concentration of $100{\mu}g/ml$ (non-cytotoxic concentration), respectively. BPE also decreased iNOS protein and COX-2 protein in LPS-induced RAW264.7 macrophages. EMSA demonstrated that BPE inhibited the DNA binding activity of the NF-kB. Conclusions : These results suggest that BPE inhibits NF-${\kappa}B$-mediated gene expression and downregulates inflammatory mediator production in RAW264.7 macrophages.

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