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Bioequivalence of Broadcef Capsule to Cefradine Yuhan Capsule (Cephradine 500 mg) (유한세프라딘 캅셀(세프라딘 500 mg)에 대한 브로드세프 캅셀의 생물학적 동등성)

  • Cho, Hea-Young;Lee, Suk;Kang, Hyun-Ah;Oh, In-Joon;Lim, Dong-Koo;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.3
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    • pp.215-221
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    • 2002
  • Cephradine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequivalence of two cephradine capsules, Cefradine Yuhan (YuHan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $23.10{\pm}2.90$ years in age and $67.69{\pm}8.04\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephradine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AVC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of 1og(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.02)\;and\;log(0.88){\sim}log(1.13)\;for \;AVC_t\;and\;C_{max},\;respectively)$. The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g., \;-17.54{\sim}7.78\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.

Static Worst-Case Execution Time Analysis Tool for Scheduling Primitives about Embedded OS (임베디드 운영체제의 스케줄링 프리미티브를 고려한 정적 최악실행시간 분석도구)

  • Park, Hyeon-Hui;Yang, Seung-Min;Choi, Yong-Hoon
    • Journal of KIISE:Computing Practices and Letters
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    • v.13 no.5
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    • pp.271-281
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    • 2007
  • Real-time support of embedded OS is not optional, but essential in contemporary embedded systems. In order to achieve these system#s real-time property, it is crucial that schedulability analysis for tasks having its property have been accomplished before system execution. Acquiring Worst-Case Execution Time(WCET) of task is a core part of schedulability analysis. Because traditional WCET tools analyze only its estimation of application task(i.e. program), it is not considered that application tasks are affected by scheduling primitives(e.g. scheduler, interrupt service routine, etc.) of OS when it schedules them. In this paper, we design and implement WCET analysis tool which deliberates on scheduling primitives of system using embedded Linux widely used in embedded OSes. This tool can estimate either WCET of normal application programs or corresponding primitives which have an influence on schduling property in embedded Linux kernel. Therefore, precision of estimation about schedulability analysis is improved. We develop this tool as Eclipse#s plug-in to work properly in any platform and support convenient interface or functionality for user.

Sodium Dependent Taurine Transport into the Choroid Plexus, the Blood-Cerebrospinal Fluid Barrier

  • Chung, Suk-Jae;Ramanathan, Vikram;Brett, Claire M.;Giacomini, Kathleen M.
    • Journal of Pharmaceutical Investigation
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    • v.25 no.3
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    • pp.7-20
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    • 1995
  • Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

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Bioequivalence of Levopid Tablet to Levopride Tablet (Levosulpiride 25 mg) (레보프라이드 정(레보설피리드 25 mg)에 대한 레보피드 정의 생물학적 동등성)

  • Cho, Hea-Young;Kang, Hyun-Ah;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.2
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    • pp.127-133
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    • 2002
  • Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

Bioequivalence of Hanacef Capsule to Duricef Capsule (Cefadroxil 500 mg) (듀리세프 캅셀(세파드록실 500 mg)에 대한 하나세프 캅셀의 생물학적 동등성)

  • Cho, Hea-Young;Lee, Suk;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.2
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    • pp.135-140
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    • 2002
  • Cefadroxil is a semi-synthetic cephalosporin active against many Gram-positive and Gram-negative bacteria. The drug has been used for the treatment of the urinary and respiratory tract infections when caused by susceptible strains of the designated microorganism. The purpose of the present study was to evaluate the bioequivalence of two cefadroxil capsules, Duricef (Bo Ryung Pharmaceutical Co. Ltd.) and Hanacef (Korean Pharmaceutical Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cefadroxil release from the two cefadroxil capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $21.58{\pm}2.43$ years in age and $70.74{\pm}10.29$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cefadroxil was orally administered, blood was taken at predetermined time intervals and the concentrations of cefadroxil in serum were determined using HPLC with UV detector. The dissolution profiles of two cefadroxil capsules were very similar at all dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Duricef were 0.05%, -5.29% and 4.53%. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.95){\sim}log(1.05)\;and\;log(0.87){\sim}log(1.02)$ for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${pm}20%$ $(e.g.,\;-6.75{\sim}15.74\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Hanacef capsule is bioequivalent to Duricef capsule.

Evaluation on Anti-Dermatophyte Effect of Larix (kaempferi) Essential Oil on the Morphological Changes of Eermatophyte Fungal Hyphae (피부사상균 균사의 형태학적 변화를 통한 일본잎갈나무 정유의 항진균 활성 효과 구명)

  • Kim, Seon-Hong;Lee, Su-Yeon;Hong, Chang-Young;Jang, Soo-Kyeong;Lee, Sung Suk;Park, Mi-Jin;Choi, In-Gyu
    • Journal of the Korean Wood Science and Technology
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    • v.41 no.3
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    • pp.247-257
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    • 2013
  • This study was to investigate the antifungal activity of Larix kaempferi essential oil against dermatophytes, Epidermophyton floccosum, Trichophyton mentagrophytes and Trichophyton rubrum. The active components of L. kaempferi against dermatophytes were determined (characterized by GC-MS), and the morphological changes of the dermatophytes exposed to the L. kaempferi essential oil were observed by electron microscope. Main component of L. kaempferi essential oil was (-)-bornyl acetate. In antifungal activity tests, MIC of L. kaempferi crude oil was 125 ppm on every fungi and 100% (agar dilution method) at more than 500 ppm. By using SEM and TEM, the fungal morphology of E. floccosum exposed to the L. kaempferi essential oil was different from that of normal hyphal morphology. Hyphae exposed to the L. kaempferi essential oil was damaged with distorted and collapsed surfaces. In addition, there were destruction and disorganization of organelles in cytoplasm and collapse of cell membrane. Active antifungal components from L. kaempferi essential oil were identified as terpene alcohol compounds like (-)-${\tau}$-muurolol, (+)-terpinen-4-ol, ${\alpha}$-terpineol, and ${\alpha}$-cadinol.

Effects of Aqua-Acupuncture of Yukmijihwangtang and Palmijihwangtang Water Extracts on the Renal Function (육미지황탕(六味地黃湯)및 팔미지황탕(八味地黃湯)의 약침(藥鍼)이 신장기능(腎臟機能)에 미치는 영향(影響))

  • Lee Moon-Ho;Son In-Chul
    • Journal of Acupuncture Research
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    • v.15 no.2
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    • pp.255-277
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    • 1998
  • The aim of this experiment was to investigate the effects of Aqua-Acupuncture of Yukmijiwangtang(六味地黃湯) and Palmijihwang-tang(八味地黃湯) water extracts applied at the meridian points BL 23(賢兪) and GV 4(命門) to test the renal function in normal rats. The results obtained were as follows; 1. Among the effects of Aqua-Acupuncture of Yukmijihwangtang water extract at the merdian point BL 23 group, there were significant changes in water balance and urine volume over a 1 week period; Both decreasing and decreasing trends were exihibited. Urinary excretion of sodium and free water clearance changed significantly over a 2 week period; Both decreasing and increasing trends were exihibited, Urinary excretion of potassium, chloride and creatinine, plasma renin activity, plasma levels of aldosterone and atrial natriuretic peptide showed no significant differences compared to the contral group. 2. Among the effects of Aqua-Acupuncture of Palmljihwangtang water extract at the merdian point BL 23 group, there were significant changes in water balance and free water clearance over a 2 week period; a decreasing trend. Urinary excretion of creatinine changed significantly over a 2 week period; an increasing trend. Urinary excretion of chloride changed significantly over 1 week period; an increasing trend. The plasma levels of atrial natriuretic peptide changed significantly over 1 and 2 week period; an increasing trend. Urine volume, urinary excretion of sodium and pottasium, plasma renin activity and plasma level of aldosterone showed no significant differences compared to the control group. 3. Among the effects of Aqua-Acupuncture of Yukmijihwangtang water extract at the meridian point GV 4 group, there was significant decrease in water balance over a 2 week period; there was significant decrease in urine volwne and urinary excretion of sodium and creatinine over a 1 week period, followed by an increasing trend after 2 weeks. Urinary excretion of free water clearance demonstrated significant changes over both 1 and 2 week period; both increasing and decreasing trends were exihibited. Urinary excretion of chloride and plasma levels of aldosterone increased significantly over 1 and 2 week period. Plasma levels of atrial natriuretic peptide also decreased significantly. Plasma renin activity showed no significant differences compared to the control group. 4. Among the effects of Aqua-Acupuncture of Palmijihwangtang water extract at the meridian point GV 4 group, water balance and urinary excretion of chloride, plasma levels of aldosterone decreased significantly over both 1 and 2 week period. Urine volume and urinary excretion of pottasium decreased significantly. Urinary excretion of creatinine and urinary excretion of sodium changed significantly over both 1 and 2 week period. Urinary excretion of free water clearance, plasma renin activity and plasma level of atrial natriuretic peptide showed no significant differences compared to the control group. Seeing these results, I come to know that the effects Aqua-Acupuncture of Yukmijihwangtang and Palmijihwangtang water extracts at the meridian point BL 23 and GV 4 have affected the renal function differently. Seeing the results that BL 23 is a meridian point for Aqua-Acupuncture directly related to the kidney, I think, we can use Aqua-Acupuncture of Yuk-mijihwangtang and Palmijihwangtang water extracts to prevent and to treat the diseases related to kidney.

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Effects of Cheunggihwadamhwan Extract on Lowering Lipid, Antioxidation and Production of Proinflammatory Cytokines in Rats Fed on High Fat Diet (청기화담환(淸氣化痰丸) 추출물이 비만쥐의 지질강하, 항산화효과 및 전염증성 Cytokines 생산에 미치는 영향)

  • Lee, Han;Park, Won-Hyung;Cha, Yun-Yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.2
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    • pp.1-13
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    • 2014
  • Objectives The purpose of this study was to investigate the effects of Cheunggihwadamhwan (CGHDH) extract on lowering lipid, antioxidation and production of proinflammatory cytokines in rats fed on high fat diet. Methods 40 Male Sprague-Dawley rats were fed on high fat diet for 8 weeks and 32 rats (above 400 g) were randomly divided into 4 groups (8 mice in each group) : control group, 100 mg/Kg CGHDH group, 200 mg/Kg CGHDH group, 300 mg/Kg CGHDH group. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And We fed each experimental group of rats basal diet and administered an extract of Cheunggihwadamhwan extracts (100 mg/kg, 200 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid in plasma and liver, concentration of proinflammatory cytokines, antioxidative activity and gene expression. The gene expression level was investigated by the way of reverse transcription-polymerase chain reaction (RT-PCR). Results 1. Concentration of plasma FFA, plasma TG, plasma total cholesterol and plasma LDL-cholesterol showed a significant decrement in Cheunggihwadamhwan groups. However, concentration of plasma HDL-cholesterol showed a significant increment in 200, 300 mg/kg Cheunggihwadamhwan groups. 2. Concentration of liver total cholesterol and liver TG showed a significant decrement in Cheunggihwadamhwan groups. 3. Concentration of plasma TBARS showed a significant decrement in all Cheunggihwadamhwan groups. Concentration of liver TBARS showed a significant decrement in 200, 300 mg/kg Cheunggihwadamhwan groups. Concentration of liver GSH-Px, SOD and CAT showed a tendency to decrease in all Cheunggihwadamhwan groups. 4. Concentration of plasma IL-$1{\beta}$, plasma IL-6, TNF-$\alpha$ and NO, showed a tendency to decrease in all Cheunggihwadamhwan groups. Concentration of plasma IL-10 showed a tendency to increase in all Cheunggihwadamhwan groups. 5. In the analysis of reverse transcription-polymerase chain reaction (RT-PCR), the gene expression of Apo-B and Apo-E in the Cheunggihwadamhwan groups showed a low expression than that of control group. The ratio of Apo-B expression per $\beta$-actin expression in the showed a significant decrement in all Cheunggihwadamhwan groups. The ratio of Apo-E expression per $\beta$-actin expression in the showed a significant decrement in 300 mg/kg Cheunggihwadamhwan groups. Conclusions According to this study, the extract of Cheunggihwadamhwan showed a positive effect of lowering lipid, antioxidation and a control of producing proinflammatory cytokines.

Spin-Flop of α-Fe2O3 Nano Particles (α-Fe2O3 나노 입자에서 Spin-Flop에 관한 연구)

  • Sur, Jung-Chul;Park, Chul-Jin;Choi, Jung-Wan;Gee, S.H.;Hong, Y.K.
    • Journal of the Korean Magnetics Society
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    • v.14 no.5
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    • pp.169-173
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    • 2004
  • We have synthesized monodispersed $\alpha$-F $e_2$ $O_3$ nano particles to investigate the spin change during the Morin transition temperature( $T_{M}$). The particle size was founded to have a very uniform distribution of 80 nm by x-ray diffraction and size dispersion analyzer. The Mossbauer spectra between the 4.2 K and the room temperature show that $T_{M}$ was shifted and the spin states of Fe ion were changed with the particle size. The Morin transition temperature of bulk usually quoted in literature is 265 K but, it decreases with the size and no transition was found at the critical size down to 4.2K. The spin direction of 80 nm sized particles are normal to the hexagonal c-axis above the $T_{M}$ and are tilted about 28~29$^{\circ}$ below $T_{M}$, which is the [110] direction of rombohedral structure.

고등식물에 미치는 항생물질의 영향 (제4보) - 대두 Aminoacid metabolism에 미치는 항생물질의 영향에 대하여

  • 이민재;이영록
    • YAKHAK HOEJI
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    • v.3 no.1
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    • pp.4-9
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    • 1957
  • Effects of antibioties on micro-organism have been reported by many scientists, such as Krampitz and Werkman, Fisher, Gale and Rodwell, Klimick Cavalito and Bailey, Umbreit, etc. On the mechanism by which penicillin act, Fisher(1947), Platt(1947), and Cavallito, considered that penicillin might act on bacteria by inhibiting with the normal function of SH-group of glutathione in the metabolism of the cell. Resenbrance of penicillin to gultathione in structure and the inactivation of penicillin by cysteine make us approve of the above inhibiting theory of SH-group. Galland (1947) and Schmidt (1947) reported that penicillin inhibited the activity of ribonuclease, Phosphatase, and mononucleotidase. Gale (1948) discovered that the gram positive bacteria had lost the power to uptake glutamic acid by ribonucleic acid in the medium contained penicillin: growth of gram positive organism was inhibited by the results that penicillin inhibited the uptake of amino acid byribonucleic acid, acting on ribonucleic acid of gram positive bacteria. Hotchkiss (1950) cultured S. aureus in the medium contained glucose and amino acids, and studied the effect of penicillin on protein synthesis. Peptide formation in living cells was inhibited by penicillin, while amono acid was utilized as before the addition of penicillin. On the otherhand, Binkley (1951) found penicillin interfered hydrolase of glutath one, and Hans (1950) reported penicillin inhibited the transpeptidation. On the machanism by which streptomycin acts. Cohen (1947) reported steptomycin made a irreversible complex with desoxyribonucleic acid, by the fact that desoxyribonucleic acid formed the precipitates with diguanide group of steptomycin. Zeller (1951) reported, on the other hand, streptomycin inhibited diamine oxidease. Geiger (1947) and Umbreit (1949) reported that steptomycin inhibited condensation of oxaloacetate and pyruvate in E. Coli and Oginsky et al (1949) reported steptomycin inhibited oxaloacetate-pyruvate reaction in Kreb's cycle. On the mechanism by which terramycin acts, Hahn & Wisseman (1951) reported that the formation of adaptive enzyme was inhibited by terramycin in E. Coli cultivated in the medium contained loctose, and that the protein synthesis was inhibited by terramycin. However, effects of antibiotics on amino acid metabolism have not been discussed much in spite of its important role in living cells. Especislly, effects of anitibiotics on higher plants have scarcely been reported. Here, to prove the effect of antibiotics on higher plants, and the mechanism by which, through amino acid metabolism, they promote or inhibit growth of plants, amino acids in bean plants treated with penicillin, streptomycin, and terramycin were analyzed by paper chromatography. And to clarify the antagonis of cysteine (as SH-group) against penicillin, through amino acid metabolism, amino acids in bean plants treated with cystene and penicillin, at the same time, were also analyzed.

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