• Title/Summary/Keyword: Dose-response

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Study on Role of Platelet Aggregation in Cerebrovascular Disease (뇌졸중증(腦卒中症)에 있어서 혈소판(血少板) 응집( 凝集)의 역할에 관한 연구(硏究))

  • Hong, Ki-Whan;Lee, Won-Suk
    • The Korean Journal of Pharmacology
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    • v.18 no.2
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    • pp.15-25
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    • 1982
  • It was undertake to investigate the factors involved in the micro thrombus formation in the plasma from the patients with cerebrovascular disease(CVD) and the in vitro actions of sodium nitroprusside on the platelet aggregate formation. 1) The microthrombus formation in the plasma from CVD was significantly enhanced, in comparison with that from the healthy volunteers. 2) Both lipid peroxide and cathepsin D in the plasma from CVD were higher than those levels from the healthy volunteers. 3) Whereas the platelets from healthy individuals showed less aggregation activity in response to ADP in the second phase those from CVD revealed the enhanced aggregating response to ADP. 4) When the bovine basilar artery, rabbit aorta and human umbilical artery were pretreated with $K^+-free$ PSS, ouabain, 13-hydroperoxylinoleic acid(13-HPLA) and cadmium they markedly enhanced the platelet aggregability respectively. 5) Platelet aggregation induced by $K^+-free$ PSS-treated bovine basilar artery was decreased by sodium nitroprusside in a dose-dependent manner, but not by either hydralazine. 6) Both dibutyryl cyclic AMP and 8-bromo cyclic GMP had the inhibitory action on the platelet aggregation. However, the latter had more prominent action than former. The antiaggregating effect by sodium nitroprusside was antagonized by pretreatment with methylene blue, but not by hemoglobin. These results provide the evidences for the therapeutic use of sodium nitroprusside in the emergency of cerebrovascular disease and in remains the further study of the clinical therapy with it.

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Glutamate-and NMDA-induced calcium influx at synaptosomes and the difference of their actions (Glutamate와 NMDA에 의한 Synaptosome에서의 칼슘 유입과 이들의 작용의 차이)

  • Lee, Chung-Soo;Sim, Jae-Keon;Shin, Yong-Kyoo;Lee, Kwang-Soo
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.71-81
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    • 1988
  • Glutamate and aspartate may evoke an increase in membrane permeability to monovalent cations and $Ca^{++}$. However, it is uncertain whether $Ca^{++}$ influx is mediated by voltage dependent $Ca^{++}$ channels or by excitatory amino acid activated channels. In addition, the influences of excitatory amino acids on $Ca^{++}$ uptake by neuronal tissues as well as the responses of their actions to extracellular $Mg^{++}$ concentration are different. $K^{+}$ induced $Ca^{++}$ uptake by synaptosomes was dependent on extracellular $Mg^{++}$ up to 5 mM and at concentration of 10 mM, $Ca^{++}$ influx was rather reduced. In $Na^{+}$ rich media, glutamate-and aspartate-induced $Ca^{++}$ uptake was increased by $Mg^{++}$ in a dose independent manner. However, the response for NMDA was inhibited by $Mg^{++}$ at concentrations above 2 mM. $K^+$-and glutamate-induced $Ca^{++}$ influx s were inhibited by 2,4-dinitrophenol, chlorprom-azine and verapamil but not by tetraethylammonium chloride. Tetrodotoxin effectively inhibited the action of glutamate but did not affect that of $K^+$. The response for MNDA was inhibited by 2, 4-dinitrophenol and tetrodotoxin, slightly inhibited by verapamil, and not affected by tetraethylammonium chloride. In $Na^{++}$ rich medium, depolarizing action of glutamate, aspartate and MNDA on synaptosomes was not demonstrated, whereas these agents stimulated $Ca^{++}$ uptake and caused $Ca^{++}$ influx induced depolarization at mitochondria. On the other hand, the activities of synaptosomal ATPases were not affected by excitatory amino acids at 5 mM. The results suggest that glutamate or NMDA induced $Ca^{++}$ influx at synaptosomes exhibits different responses for extracellular $Mg^{++}$ Ex citatory amino acids induced $Ca^{++}$ influx at synaptosomes may be associated with increased permeability of membrane for $Na^{++}$ and $Ca^{++}$ except $K^{++}$ and membrane depolarization due to increased ionic permeability.

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The effect of lime on the potassium requirement for low land paddy (석회(石灰)의 시용(施用)이 수도작(水稻作)에서의 가리소요량(加里所要量)에 미치는 영향(影響))

  • Oh, Wang Keon;Lee, Sang Bum;Park, Chan Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.5 no.2
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    • pp.39-42
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    • 1972
  • A field experiment was conducted in a moderately well drained paddy field doveloped in a narrow strip of a valley in order to observe changes of potassium requirement in paddy production when lime is applied. The results obtained are as follows; 1. The response of paddy to potassium (K) and lime (L) is represented mathematically as follow; $Y=462.78+11.582K-0.058L-0.768K^2-0.000015L^2+0.2204KL$. It is considered that the increase of potassium reqirement when slaked lime is applied, is partially due to the increased growth of plant accomplished by the improvement of soil conditions such as the reduction of respiration inhibitors and cationic balance in soil solution. 2. An economic analysis of the use of potassium and slaked lime applying the costs, 80 won per kg of paddy, 19 won per kg of potassium and 4 won per kg of slaked lime to the response function above, showed that the slaked lime without potssium brought a large loss, whereas the use of the lime together with potassium increased the profit remarkably. The profit increased when 10kg of potassium per 10 a is applied in addition to 200kg slaked limn, per 10kg is amounted 4,685 won. 3. A linear relationship between the economic optimum dose of potassium (y) and the amount of slaked lime (x) in paddy production, is obtained as follow; $$y=7.48+\frac{2.77}{200}x$$ It is, however, considered that the amount of potassium to he used might differ according to the soil conditions such as the potassium content and cation exchange capicity of the soil.

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P53 Overexpression and Outcome of Radiation Therapy in Head & Neck Cancers (두경부종양 환자에서 p53의 과발현과 방사선치료결과)

  • Kim In Ah;Choi Ihl Bhong;Kang Ki Mun;Jang Ji Young;Kim Kyung Mi;Park Kyung Shin;Young Shin Kim;Kang Chang Suk;Cho Seung Ho;Kim Hyung Tae
    • Radiation Oncology Journal
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    • v.17 no.1
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    • pp.1-8
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    • 1999
  • Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

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A BIOCHEMICAL INVESTIGATION OF THE ROLE OF $IL-1{\beta}$ UPON INFlAMMATION IN MOUSE (마우스에서 $IL-1{\beta}$가 염증의 발현에 미치는 영향에 관한 연구)

  • Yoon, Duk-Sang;Lee, Ki-Soo
    • The korean journal of orthodontics
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    • v.28 no.4 s.69
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    • pp.611-626
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    • 1998
  • Cytokines are intercellular peptide mediators that regulate homeostasis and host defense reactions in living body. Of the diversity of cytokines in terms of biological accomplishment, interleukin $1-{\beta}$($IL-1{\beta}$) and tumor necrosis factor(TNF) are the most conspicuous cytokines with a wide variety of effects on cells involved in inflammatory and immune responses, and likely to be involved in the inflammatory pathogenesis of oral tissue as well. The present study was designed to explicate the role of $IL-1{\beta}$ on inflammatory revelation of oral tissues in mice biochemically. In the Induced arthritis by injection of 10${\mu}g$ LPS shown the relaese of 0.93 ${\mu}g$ $IL-1{\beta}$/joint with a peak at at 4-5 h. and diminished at 24t and the release of $TNF_{\alpha}$ of 1.25 ${\mu}g$/joint with a peak at 2-3h and diminished at 6h. After injection of th $IL-1{\beta}$ into the joint, the mumber of leucocytes proliferated with a peak at 4-5h and diminished at 36h and the loss of proteoglycan showed with maximum at 15-30h. After injection of $IL-1{\beta}$ into the oral tissue, cycloosygenase metabolites ($PGE_2$) accumulated in the oral tissue with dose dependant. These elucidated $IL-1{\beta}$ to be inflammatory mediator in the early phase of its pathogenesis. Intraoral injection of recombinant $IL-1{\beta}$ induced the proliferation of leukocytes in situ. $IL-1{\beta}$ took an pertinent part in the development of inflammation and the succession of cellular infiltration. The results exemplify that $IL-1{\beta}$ plays a significant role in mediating inflammatory response induced by LPS in oral tissue, the inflammatory response is regulated by $IL-1{\beta}$ at an acute phase of pathogenesis.

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The Effects of Vitamin C on the Activity of Liver Enzymes and Hepatic Damage in Rats Treated with Radiation and Aflatoxin $B_1$ (Vitamin C가 방사선과 Aflatoxin $B_1$을 투여한 흰쥐의 간 기능 효소 활성 및 간 손상에 미치는 효과)

  • Kang, Jin-Soon
    • The Korean Journal of Food And Nutrition
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    • v.23 no.1
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    • pp.30-38
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    • 2010
  • This study was conducted to determine the effects of vitamin C on the activity of liver function enzymes and electromicrographic changes in white rats treated with aflatoxin $B_1(AFB_1)$ or X-ray and $AFB_1$. Six week-old male Sprague-Dawley rats were randomly divided into five groups: a control group, $AFB_1$ treated group, $AFB_1$ treated group with vitamin C, X-ray and $AFB_1$ co-treated group, X-ray and $AFB_1$ co-treated group with vitamin C. On the first day of the experiment, only one dose of X-rays was exposed to the entire liver at 1,500 cGy. Next, vitamin C was injected at 10 mg/kg body weight by intraperitoneal injection, followed 1 hr later by the administration of 0.4 mg/kg of $AFB_1$ by intraperitoneal injection. These treatments were then administered every three days over a period of 15 days. On the 16th day of treatments, the animals were sacrificed. Analysis of the activity of the liver function enzymes, GOT, ALK phatase and LDH, in the sera of rats revealed that they were somewhat increased by $AFB_1$ treatment, X-ray and $AFB_1$ co-treatment when compared to the control group. Furthermore, the activity of these enzymes decreased in response to administration of vitamin C. Especially, the levels of GOT were remarkably decreased in the $AFB_1$ treated group treated with vitamin C when compared to the group treated with $AFB_1$ alone(p<0.001). Electromicrographic analysis revealed cloudy swelling, necrosis, vesicular degeneration and fat accumulation of hepatocytes in response to treatment with $AFB_1$ or co-treatment with X-ray and $AFB_1$. However, the destruction of hepatic cells was considerably lower in the vitamin C-treated group. These results indicate that vitamin C had ameliorating effects on the hepatic cell damage.

Preliminary Result in Patients with Primary Hepatoma Treated by Stereotactic Radiotherapy (원발성 간암에 대한 정위방사선치료의 예비결과)

  • Kang Ki Mun;Choi Ihl Bohng;Kim In Ah;Choi Byung Ock;Kang Young Nam;Chai Gyu Young;Han Sung Tae;Chung Gyu Won
    • Radiation Oncology Journal
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    • v.19 no.1
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    • pp.34-39
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    • 2001
  • Purpose : It is not common to evaluate the response of the fractionated stereotactic radiotherapy (SRT) to primary hepatoma as compared with conventional radiotherapy. The purpose of the study was to take the preliminary result on the clinical trial of primary hepatoma by SRT. Materials and Methods : From July 1999 to March 2000, thirty three patients were hospitalized in the St. Mary's Hospital, and treated with SRT for extracranial tumors. Among them, 13 patients were diagnosed to primary hepatoma and then applied by frameless SRT using 6 MV linac accelerator. There were 12 male and 1 female patients. They had the age of $ 44\~66$ year old (median : 59) and the tumor size of $10\~825\;cc$ (median : 185 cc). SRT was given to them $3\~5$ fractions a week (5 Gy/fraction, $90\%$ isodose line) for $2\~3$ weeks. Median dose of SRT was 50 Gy and the range was $30\~50\;Gy$. Results : Follow-up period ranged from 3 months to 13 months with median of 8 months. After treating SRT to thirteen patients with primary hepatoma, the response of the tumor was examined by abdominal CT : they are classified by 1 complete regression $(7.7\%)$, 7 partial regression $(53.8\%)$, 4 minimal regression $(30.8\%)$, 1 stable disease $(7.7\%)$. The positive responses more than partial remission were 8 patients $(61.5\%)$ after the treatment. The level of serum alpha-fetoprotein (AFP) after the treatment as compared with pretreatment had been $92.3\%$ decreased. There was no severe complication except dyspepsia $84.6\%$, mild nausea $69.2\%$, transient decreased of hepatic function $15.4\%$ and fever $7.7\%$. Conclusion : SRT to the patients with primary hepatoma was potentially suggested to become the safe and more effective tool than the conventional radiotherapy even though there were relatively short duration of follow-up and small numbers to be tested.

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External Beam Radiotherapy Alone in Advanced Esophageal Cancer (진행된 식도암의 방사선 단독치료 성적)

  • Ahn Sung Ja;Chung Woong Ki;Nah Byung Sik;Nam Taek Keun
    • Radiation Oncology Journal
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    • v.18 no.1
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    • pp.11-16
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    • 2000
  • Purpose :We peformed the retrospective analysis to find the outcome of external beam radiotherapy alone in advanced esophageal cancer patients. Methods and Materials : One hundred and six Patients treated with external beam radiotherapy alone between July 1990 and December 1996 were analyzed retrospectively. We limited the site of the lesions to the thoracic esophagus and cell type to the squamous cell carcinoma. Follow-up was completed in 100 patients (94$\%$) and ranged from 1 month to 92 months (median; 6 months). Results :The median age was 62 years old and male to female ratio was 104 2. Fifty-three percent was the middle thorax lesion and curative radiotherapy was peformed in 83$\%$. Mean tumor dose delivered with curative aim was 58.6 Gy (55$\~$70.8 Gy) and median duration of the radiation therapy was 53 days. The median survival of all patients was 6 months and )-year and 2-year overall survival rate was 27$\%$ and 12$\%$, respectively, Improvement of dysphagia was obtained in most patients except for 7 patients who underwent feeding gastrostomy. The complete response rate immediately after radiation therapy was 32$\%$ (34/106). The median survival and 2-year survival rate of the complete responder was 14 months and 30$\%$ respectively, while those of the nonresponder was 4 months and 0$\%$ respectively (p=0.000). The median survival and 2-year survival rate of the patients who could tolerate regular diet was 9 months and 16$\%$ while those of the patients who could not tolerate regular diet was 3 months and 0$\%$, respectively (p=0.004). The survival difference between the patients with S cm or less tumor length and those with more than 5 cm tumor length was marginally statistically significant (u=0,06). However, the survival difference according to the periesophageal invasion or mediastinal tyrnphadenopathy in the chest CT imaging study was not statistically significant in this study. In a multivariate analysis, the statistically significant covariates to the survival were complete response to radiotherapy, tumor length, and initial degree of dysphagia in a decreasing order. The complication was observed in 10 patients (9$\%$). Conclusion :The survival outcome for advanced esophageal cancer patients treated by external beam radiotherapy alone was very poor. In the treatment of these patients, the brachytherapy and chemotherapy should be added to improve the treatment outcome.

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$HgCl_2$ Dysregulates the Immune Response of Balb/c Mice (수은에 의한 마우스의 면역반응 조절장애)

  • Ki, No-Suk;Koh, Dai-Ha;Kim, Chong-Suh;Lee, Jung-Sang;Kim, Nam-Song;Lee, Hwang-Ho
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.1 s.45
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    • pp.11-24
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    • 1994
  • The studies reported here were undertaken to investigate the effects of mercury chloride on immune system of Balb/c mouse employing a flexible tier of in vitro and in vivo assays. Mercury chloride inhibited the proliferative responses of spleen cells to lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin as a dose-dependent manner. This inhibitory effect was observed not only when $HgCl_2$ was added 2nd or 3rd day of 3 days culture period but also when spleen cells was pretreated with $HgCl_2$ for 2 hours. Mercury chloride, however, potentiated the production of IgM and IgG from spleen cells. During the $HgCl_2$ administration by drinking for 3 weeks, the weight gain of mice was significantly blunted than that o control group mice, while no overt signs related to mercury toxicity were noted in any mice of experimental group. There was no change in thymus and spleen weights, and in histological findings of kidney, bone marrow of femur, thymus, spleen, and popliteal lymph node after 3 weeks of mercury exposure. However, $HgCl_2$ induced a significant increase of total serum IgM, IgG including $IgG_1,\;IgG_{2a}\;and\;IgG_{2b}$, and IgE in Balb/c mice. Treatment in vivo with anti-IL-4 monoclonal antibody significantly abrogated the $HgCl_2$-induced increase in total serum IgG1 and IgE. Whereas $HgCl_2$ potentiated total serum IgM and IgG, there was no difference in total serum hemagglutinin to SRBC (Sheep Red Blood Cell) between experimental and control group mice when these mice were immunized with SRBC. All these findings observed in Balb/c mice suggest that mercury perturbates well-orchestrated regulation of immune responses before developing histopathological changes in lymphoid tissues.

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Effect of Timing and Placement of N Fertilizer Application for Increased Use Efficiency - Principle and Practice (열대지역(熱帶地域)에 있어서 질소비료(窒素肥料)의 시용시기(施用時期)와 시비위치(施肥位置)가 비료효율(肥料效率)에 미치는 영향(影響) - 원리(原理)와 실제(實際))

  • Hong, Chong-Woon
    • Korean Journal of Soil Science and Fertilizer
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    • v.20 no.3
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    • pp.285-299
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    • 1987
  • Timing and placement of fertilizer applications are two managerial means to improve the fertilizer use efficiency. The relative importance of these two means is determined by the application rate. With the realistic rate of N application recommended to the small farmers in the tropics, at present and in the near future, basal application in right manner, seems to be more important than split application at different times. In wetland rice soils, deep placement by whatever available means is desirable. But in the situations where perfect deep placement is very difficult to implement, the whole-layer application may be worth trying, until better methods become available. In rainfed uplands, N fertilizer application plans should be contingent upon the amount and distribution of rainfall: apply a less risky rate as subsurface banding near the crop rows to start with; then, depending upon the rainfall prospects in the season, apply or omit the additional dose. Because the patterns of crop response to N fertilizer can be significantly different between the research farms and farmers' fields, it seems imperative to have information on the patterns of crop response to N under farmers' management conditions, for the development of realistic fertilizer application recommendations. To enable the farmers to adopt improved fertilizer application technologies, it is essential to develop and make available to farmers convenient fertilizer applicators. Past experience with the improved fertilizer use technologies indicates that, in the long run, the development of fertilizers that are not only effective and convenient for farmers to use but also easy to produce without major modifications of existing fertilizer production systems is the ultimate solution to the problem of low N fertilizer use efficiency.

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