• Title/Summary/Keyword: Dose Response Curve

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Weekly irinotecan and carboplatin for patients with small cell lung cancer (소세포 폐암 환자에서 이리노테칸, 카보플라틴 주별 분할 항암요법의 효과)

  • Lee, Hye-Won;Jeong, Eu Gene;Kim, Dong Hyun;Lee, Hyuk;Kang, Bo Hyoung;Um, Soo-Jung;Roh, Meesook;Son, Choonhee
    • Journal of Yeungnam Medical Science
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    • v.31 no.2
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    • pp.82-88
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    • 2014
  • Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

LIGAND BINDING CHARACTERISTICS OF $K_2$- OPIOID RECEPTOR AND ITS ROLE IN REGULATION OF 〔$^3$H〕HISTAMINE RELEASE IN FRONTAL CORTEX OF THE RAT

  • Kim, Kee-Won-;Park, Kyu--Cho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.305-305
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    • 1994
  • It has been shown that there are several subtypes of $\kappa$ opioid receptor, We have evaluated the properties of non-${\mu}$, non-$\delta$ binding of 〔$^3$H〕DIP, a nonselective opioid antagonist, in rat cortex membranes. Binding to ${\mu}$ and $\delta$ sites was inhibited by the use of an excess of competing selective agonists (DAMGO, DPDPE) for these sites. (-)Ethylketocyclazocine(EKC) inhibited 〔$^3$H〕DIP binding with Ki. of 70 nM. However, arylacetamides (U69593 and U50488H) gave little inhibition. Also, we have examined the opioid modulation of K$\^$+/(30 mM)-induced histamine release in rat frontal cortex slices labeled with 1-〔$^3$H〕histidine. The 〔$^3$H〕histamine release from cortex slices was inhibited by EKC, a $\kappa$$_1$-and $\kappa$$_2$-agonist, in a concentration-dependent manner(10 to 10,000 nM). The IC$\sub$50/ of EKC was 107 ${\pm}$ 6 nM. However, the $\delta$ receptor selective agonists, DPDPE and deltorphine II, ${\mu}$ receptor agonists, DAMGO and TAPS, $\kappa$$_1$-agonists, U69593 and U50488H, and $\varepsilon$-agonist, ${\beta}$-endorphin, did not inhibit histamine release even in micromoiar dose, indicating that ${\mu}$, $\delta$ or $\kappa$$_1$ receptors are not involved. The concentration-response curve of EKC was shifted to right in the presence of naloxone (300 nM), a ${\mu}$ preferential antagonist, norbinaltorphimine(300 nM), a $\kappa$$_1$ preferential antagonist and bremazocine(1 nM), a $\kappa$$_1$-agonist and $\kappa$$_2$-antagonist. These results suggest that $\kappa$$_2$ opioid receptor regulates histamine release in the frontal cortex of the rat.

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Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women

  • Chang, Youngeun;Choue, Ryowon
    • Nutrition Research and Practice
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    • v.7 no.5
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    • pp.393-399
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    • 2013
  • Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group ($2,101{\pm}352ng{\cdot}h/mL$) was significantly smaller than those of the isogen ($2,628{\pm}573ng{\cdot}h/mL$) and fermented soybean ($2,593{\pm}465ng{\cdot}h/mL$) groups. The maximum plasma concentration ($C_{max}$) of daidzein for the soymilk group ($231{\pm}44$ ng/mL) was significantly higher than those of the isogen ($160{\pm}32$ ng/mL) and fermented soybean ($195{\pm}35$ ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.

Mechanism of Endothelium dependent Relaxation induced by $Mg^{++}-deficiency$ in isolated Canine Coronary Arteries (개의 관상동맥에서 $Mg^{++}$ 결핍에 의한 혈관 확장반응의 기전)

  • Ann, Hyung-Soo
    • YAKHAK HOEJI
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    • v.33 no.1
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    • pp.1-9
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    • 1989
  • We have recently reported that $Mg^{++}-deficiency$ showed endothelium dependent relaxation in isolated canine coronary arteries precontracted with $PGF_{2{\alpha}}$. To differentiate the release of EDRF or $PGI_2$ from the endothelium cells as the cause of vasorelaxation by $Mg^{++}-deficiency$, effects of several inhibitors of arachidonic acid metabolism on the relaxation by $Mg^{++}-deficiency$ were evaluated and also compared with that of acetylcholine. Ibuprofen and tranylcypromine ($10{\mu}M$), an inhibitor of cyclo-oxygenase and $PGI_2$ synthetase, respectively, did not effect on $Mg^{++}-free$ induced vasorelaxation. Pretreatment of quinacrine ($10{\mu}M$), an inhibitor of phospholipase $A_2$ and also $Ca^{++}$ uptake, blocked vasorelaxation by $Mg^{++}-free$. But trifluoperazine ($10{\mu}M$), which is about as potent as quinacrine in the inhibition of $Ca^{++}$ uptake, did not effect on $Mg^{++}-deficiency$ induced vasorelaxation. NDGA ($10{\mu}M$), an inhibitor of lipoxygenase, completely restored $Mg^{++}-free$ induced vasorelaxation, even though pretreatment of that was not blocked which might be due to the characteristics of vasorelaxation of NDGA itself. Pretreatment of methylene blue ($10{\mu}M$), which is known as a inhibitor of EDRF through the blocking effect of guanylate cyclase, completely blocked vasorelaxation by $Mg^{++}-free$ as well as acetylcholine ($0.1{\mu}M$). Acetylcholine-induced dose response curve was also antagonized by pretreatment of quinacrine ($10{\mu}M$), but not by ibuprofen, tranylcypromine and NDGA. These results appear to suggest that $Mg^{++}-free$ induced vasorelaxation was mediated by the release of EDRF through the activation of phospholipase $A_2$ and noncyclo-oxygenase on arachidonate metabolism.

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Interaction of Antihistaminics with Muscarinic Receptor (III) - Relationship between binding and functional in vitro data -

  • Lee, Shin-Woong;Park, Young-Joo
    • Archives of Pharmacal Research
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    • v.14 no.2
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    • pp.181-187
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    • 1991
  • The muscarinic antagonist 1-[benzilic 4, 4'-$[^3H]$ QUINUCLIDINYL BENZILATE $([^3H]$ QNB) bound to a single class of muscarinic receptors with high affinity in rabbit ileal membranes. The $K_D\;and\;B_{ max}$ values for $([^3H]$ QNB calculated from analysis of saturation isotherms were 52.5 pM AND 154 fmol/mg, respectively. Chlopheniramine (CHP), histamine $H_1$ blocker, increased $K_D$ vlue for $([^3H]$QNB without affecting the binding site concentrations and Hill coefficient. The $K_i$ value of CHP for inhibition of $([^3H]$QNB binding in ileal membranes was 1.44\mu{M}$ and the pseudo-Hill coefficient for CHP was close to unit. In the functional assay carbachol, muscarinic agonist, increased the contractile force of ileum with $ED_{50}$ value of $0.11\mu{M}$. CHP caused the rightward shift of the dose-response curve to carbachol. The $pA_2$ value of CHP determined from Schild analysis of carbacholinduced contraction was 5.77 and the slope was unity indicating competitive antagonism with carbachol. The dissociation constant $(K_i)$ of CHP obtained in competitive experiments with $([^3H]$ QNB was similar to the $K_A$ value (1.69 \mu{M)}$ of CHP as inhibitor of carbachol induced contraction in rabbit ileum. This result suggest that the binding of $H_i$ blocker. CHP, vs $([^3H]$QNB to muscarinic receptors in ileal membranes represents an interaction with a receptor of physiological relevance.

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Studies on the Rapid and Competitive Enzyme-linked Immunosorbent Assay for the Detection of Thyroxine (T$_4$) in Human Sera (경쟁적 효소면역측정법을 이용한 환자 혈청 내 Thyroxine (T$_4$)의 검출)

  • Sang-Wook Park;Jong-Bae Kim
    • Biomedical Science Letters
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    • v.5 no.1
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    • pp.11-15
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    • 1999
  • Thyroxine (3,5,3',5'-L-tetraiodothyronine; T$_4$) is the most commonly measured thyroid hermono for the diagnosis of various thyroid disorders. Although radioimmunoassay (RIA) is still considered as the reference technique for the measurement of T$_4$, it is generally regarded that RIA has its primary disadventages in handling the wastes and controling the human and material resources. Therefore, establishment of enzyme-linked immunosorbent assay (ELISA) has of great significance. To verify the usefulness of our enzyme immunoassay, we have obtained the standard dose response curve of T$_4$ in patient's sera which is inversely proportional to the amount of herseradish peroxidase (HRP) conjugated monoclonal antibody of T$_4$ bound to the wells. The correlation coefficient (r) between the ELISA and chemiluminescent assay was 0.444 (n=38). Thus we have investigated the establishment of rapid and sensitive competitive ELISA assay method for detection of T$_4$ in patient's sera.

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The Reactivity of Antiserum Raised against Native Glucose-6-phosphate Dehydrogenase with Denatured Glucose-6-phosphate Dehydrogenase in Competitive ELISA

  • Kim, Moon-Hee
    • BMB Reports
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    • v.31 no.5
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    • pp.519-523
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    • 1998
  • We have previously reported that anti-glucose-6-phosphate dehydrogenase (G6PD) serum raised against native G6PD (nG6PD) enzyme recognized nG6PD antigen poorly in competitive enzyme-linked immunosorbent assay (ELISA) (Kim, 1997). In the present study, we investigated whether anti-G6PD serum raised against nG6PD can react with denatured G6PD effectively in competitive ELISA. We used partially active G6PD (paG6PD) by repeated freeze-thawing or SDS-denatured G6PD (SDS-G6PD) as both immobilized and soluble antigens, and anti-G6PD serum raised against nG6PD for competitive ELISA. The polystyrene cuvettes coated with either paG6PD or SDS-G6PD were challenged with a mixture of a limiting amount of anti-G6PD serum and various doses of paG6PD or SDS-G6PD as competitors, followed by incubation with alkaline phosphatase-anti-IgG conjugate. The competitive ELISA with paG6PD or SDS-G6PD antigen exhibited the sigmoidal dose-response curve characteristic of competition immunoassays. Furthermore, Triton-denatured G6PD (Triton-G6PD) was used in competitive ELISA. The paG6PD, SDS-G6PD, or Triton-G6PD used as competitors increased the inhibition of antibody binding to immobilized either of nG6PD or denatured G6PD compared with nG6PD competitor. The inhibition by denatured G6PD competitors was more pronounced at high competitor concentrations than at low counterparts. We conclude that anti-G6PD serum raised against nG6PD can effectively react with denatured G6PD in competitive ELISA and that our anti-G6PD serum recognizes denatured enzymes better than active enzymes.

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Antihypertensive activity of Zingiber officinale and Korean ginseng in experimentally induced hypertension in rats

  • Mohan, M;Balaraman, R;Kasture, SB
    • Advances in Traditional Medicine
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    • v.7 no.3
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    • pp.261-273
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    • 2007
  • We investigated the antihypertensive effect of Pet ether extract (PE) of ginger rhizome; its toluene fraction (TF) and Korean ginseng extract (KGE) in deoxycorticosterone acetate (DOCA) - salt induced and fructose induced hypertensive rats. In DOCA model, DOCA (25 mg/kg, once a week; s.c) was administered in uninephrectomised animals for 4 w. PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were evaluated for their antihypertensive effect. In the fructose model, drinking water was replaced with fructose (10%) for five weeks to induce hypertension. PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were assessed for its antihypertensive effect in fructose model. After completion of the treatment schedule, vascular reactivity to various agonists like 5-HT, noradrenaline, adrenaline, phenylbiguanide and acetylcholine were recorded in rats of both the models. A cumulative dose response curve (CDRC) of 5-HT was carried out in isolated rat fundus strip of the fructose induced hypertensive rats. Chronic administration of PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o), and KGE (30 mg/kg/day; p.o) significantly reduced the blood pressure in DOCA salt whereas PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) reduced the blood pressure in fructose induced hypertensive rats. Treatment with PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) in fructose model for five weeks shifted the CDRC towards the right on rat fundus. The mechanism of action may partly involve the serotonergic antagonistic property.

A Study on the Proper Chest Exposure Conditions of Mobile Digital X-ray Unit by Exposure Index (Exposure Index를 이용한 이동형 디지털 X선 장치의 흉부촬영 적정노출조건에 관한 연구)

  • Kim, Jae-In;Lee, Yang-Sub;Jang, Dong-Soo;Jung, Min-Cheol;Bae, Seung-Ho;Lee, Kwan-Sub;Ha, Dong-Yoon
    • Korean Journal of Digital Imaging in Medicine
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    • v.13 no.3
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    • pp.139-144
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    • 2011
  • The purpose of this report is recommending a standard indicator which reflects the radiation exposure that is incident on a detector after every exposure event and that reflects the noise levels present in the image data. The experiment was performed with mobile digital X-ray unit and used a acrylic phantom for exposure index measurement. Exposure modality was kVp, mAs, SID. After every exposure, make a data sheet for characteristic curve of detector response. The equipment performed Mobile digital X-ray unit provide the user with values ralated to the incident exposure(air kerma)to the digital detector. They are showed as a logarithmic function shaped. As a result, DEI means a relative measure of exposure to the detector, as compared to the expected exposure for a particular anatomical view. Radiographic technique is the combination of factors used to exposure an anatomical part to produce a high quality radiography and technique charts used most commonly by radiographers to produce consistently exposure level which patient dose can be kept acceptably low.

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Role of cAMP, EGF, IGF-I and Protein Phosphorylation in Mammary Development I. Effect of EGF, IGF-I and Photoreactive Cyclic AMP on DNA Synthesis of Mammary Epithelial Cell (유선발달에 있어서 cAMP, EGF, IGF-I 및 단백질 인산화 작용의 역할 I. EGF, IGF-I 및 Photoreactive Cyclic AMP가 유선상피세포의 DNA합성에 미치는 효과)

  • 여인서;박춘근;홍병주
    • Korean Journal of Animal Reproduction
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    • v.17 no.1
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    • pp.49-56
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    • 1993
  • Mouse mammary epithelial cells(NMuMG) were plated onto 24 well phates(100,000 cells/well), in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 hours, EGF)0~100ng/ml) was added simultaneously with IGF-I(10ng/ml), 1$\mu$M photoreactive cAMP(4,5-dimethoxy-2-nitrobenzyl adenosine-3',5' cyclic monophosphate, DMNB) or IGF-I plus DMNB. After 2 hours, the cells were expposed to UV light(300nm, 3 second pulse0 in order to activate DMNB which induces a rapid transient increase in intracellular cAMP upon UV irradiation. DNA synthesis was estimated as incorporation of 3H-thymidine into DNA(1 hour pulse with 1$\mu$Ci/ml, 18~19 hours after UV exposure). Without IGF-I or DMNB, EGF(10 or 100ng/ml) increased DNA synthesis from 8,362 dpm/well in control to 16,345 or 18,684 dpm/well with EGF(pooled SE=1,239 dpm/well, P<0.05). IGF-I or IGF-I plus DMNB alone increased DNA synthesis from 8,362 dpm/well in control to 17,307 or 20,427 dpm/well, respectively(P<0.05). Addition of IGF-I, DMNB or IGF-I plus DMNB into 0~100ng/ml EGF did not significantly change the shape of dose response curve of EGF alone. In other experiment, EGF or IGF-I plus DMNB into 10ng/ml EGF group exhibited interaction effect in DNAsynthesis [EGF(10ng/ml)=18,497; IGF-I+EGF=22,837; DMNB+EGF=20,658 ; IGF-I+DMNB+EGF=29,658, pooled SE=1,055, P<0.05]. These results indicate that simultaneous activation of EGF, IGF-I and intracellular cAMP interact in DNA synthesis of mouse mammary epithelial cells.

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