• 제목/요약/키워드: PD-L2

검색결과 280건 처리시간 0.022초

실험견에서 Metoprolol 약리효과의 약동/력학적 검토 (Pharmacokinetic/Pharmacodynamic Analysis of Metoprolol in Dogs)

  • 오동진;장인진;이경훈;임동석;김형기;신상구;박찬웅;신재국
    • 대한약리학회지
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    • 제31권2호
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    • pp.251-259
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    • 1995
  • Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

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한국산(韓國産) 치과주조용(齒科鑄造用) 저금함유합금(低金含有合金)의 조성(組成) 및 기계적(機械的) 성질(性質)에 관(關)한 비교연구(比較硏究) (A COMPARATIVE STUDY ON THE CHEMICAL COMPOSITION AND MECHANICAL PROPERTIES OF FOUR LOW-GOLD-CONTENT DENTAL CASTING ALLOYS MANUFACTURED IN KOREA)

  • 장익태;양재호;김창회;김광남;이선형;김영수;장완식
    • 대한치과보철학회지
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    • 제19권1호
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    • pp.17-27
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    • 1981
  • This study was conducted to determine the chemical composition and the mechanical properties of four commercially available low gold-based crown and bridge alloy produced in Korea. Four dental casting gold-silver-palladium alloys, i.e., A, B, C and D (code of alloys) were selected for the evaluation of chemical composition, ultimate tensile strength, elongation. values and Vickers hardness. The chemical composition of test specimens was analyzed by both emission spectrography and wet gravitation method with a 1.5gm of low gold ingot. The tensile properties and Vickers hardness was determined with cast specimens treated in following three conditions; as-cast, softening heat treatment and hardening heat treatment. The tensile testing bars were cast in accordance with the model designed by Gettleman and Harrison (1969) which was modified from the A. D. A. Specification No. 14 for dental chromium-cobalt casting alloy. Nine tensile test specimens were made from a split silicone mold for each of the test alloys to the size of 2.5mm in diameter and a gauge length of 10mm. All four alloys were handled in accordance with conventional methods used in Type III gold alloys. Ultimate tensile strength and elongation were measured on an Instron Universal Tensile Testing Machine (Model 1125, Japan) operated at a crosshead rate of 0.1cm/min. Elongation values were measured using Digital Measuring Microscope (MS-152, FUSOH, Japan). Vickers hardness was determined with a Vickers Hardness Tester (Model VKH-l, Japan) at a 1.0kg load on a mounted tensile test specimen. The following results were obtained from this study; 1. All tested alloys were composed of Au, Ag, Pd, Cu, Zn and Fe in common. The composition rate of gold for all four alloys was found in the range of $42{\sim}47$ weight % as shown below. Alloy A; Au 45%, Ag 40.2%, Pd 5.76%, others 9.04%. Alloy B; Au 47.1%, Ag 29.03%, Pd 6.98%, others 16.92%. Alloy C; Au 45%, .Ag 26.9%, Pd 6.83%, others 21.07%. Alloy D; Au 41.8%, Ag 34.4%, Pd 6.95%, others 16.85%. 3. The ultimate tensile strength of the four alloys was in the range of $31{\sim}82kg/mm^2$. The test results were shown in the below order from the highest value; As-cast condition; D, B, C, A. Softening heat treament; B, C, D, A. Hardening heat treatment; D, B, C, A. 4. The test :results of the elongation rate for each alloy were in the range of $0.5{\sim}18%$. The test results were shown in the below order from the highest value; As-cast condition; A, D, B, C. Softening heat treatment; A, C, D, B. Hardening heat treatment; C, D, B, A. 5. Vickers hardness for each of the four alloys was in the range of $120{\sim}230$. The test results were shown in the below order from the highest value; As-cast condition; C, B, D, A Softening heat treatment; D, B, C, A. Hardening heat treatment; D, A, C, B. 6. There were no differences in the physical properties between as-cast condition and softening heat treatment.

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cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

  • Peng, Li-qun;Li, Ping;Zhang, Qiu-li;Hong, Lan;Liu, Li-ping;Cui, Xun;Cui, Bai-ri
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권1호
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    • pp.9-14
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    • 2016
  • Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

Angiotensin II에 의해 유도되는 활성산소발생 기전에 대한 연구 (Angiotensin II-Induced Generation of Reactive Oxygen Species Is Regulated by a Phosphatidylinositol 3-Kinase/L-Type Calcium Channel Signaling Pathway)

  • 진서연;하정민;김영환;이혜선;배순식
    • 생명과학회지
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    • 제25권2호
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    • pp.231-236
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    • 2015
  • Angiotensin II (AngII)는 혈관평활근세포의 수축을 통해 혈관을 수축시키는 강력한 작용을 나타낼 뿐만 아니라 혈관세포의 성장 등에 중요한 역할을 한다. 본 연구에서는 AngII에 의해 형성되는 활성산소가 phosphatidylinositol 3-kinase (PI3K)에 유리되는 칼슘에 의해 조절된다는 것을 검증하였다. 쥐의 대동맥으로부터 분리된 혈관평활근세포에서 AngII에 의해 활성산소가 농도 의존적, 그리고 시간 의존적으로 형성됨을 관찰하였다. AngII에 의해 형성되는 활성산소는 PI3K의 억제제에 의해 봉쇄되었으나 EKR의 억제제에 의해서는 봉쇄되지 않음을 알 수 있었다. AngII에 의해 유리되는 칼슘은 L-type 칼슘이온통로 봉쇄제인 Nifedipine 또는 배양액에 칼슘이 제거된 환경에서 억제됨을 확인할 수 있었다. 마지막으로 AngII에 의해 형성되는 활성산소는 배양액에 칼슘이 없는 조건이나 L-type 칼슘이온통로 억제제를 전처리 하였을 경우 억제되는 것을 확인하였다. 이러한 결과들을 바탕으로 쥐의 대동맥으로부터 분리된 혈관평활근세포에서 AngII에 의한 활성산소의 형성은 PI3K/L-type 칼슘이온통로를 통한 기전을 통해 조절됨을 제안한다.

Ce(OH)$_3$의 공침부선에 의한 해주중 몇 가지 미량원소의 동시 농축 및 정량 (Simultaneous Concentration and Determination of Several Trace Elements in Sea Water by Ce(OH)$_3$ Coprecipitation)

  • 성우식;최희선;김영상
    • 대한화학회지
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    • 제37권3호
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    • pp.327-333
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    • 1993
  • 침전부선법에 의한 해수중 몇 가지 미량원소이 예비농축에 관하여 연구하였으며, 농축된 원소들을 불꽃 원자흡수분광법으로 정량하였다. Cd(II), Cu(II), Fe(III), Mn(II), Pb(II) 및 Pd(II) 등의 미량원소를 정량적으로 농축하기 위하여, 해수 1.0l에 1.0M Ce(III)용액 2.0 ml를 가하고 자석젓개로 저어주면서 5.0M NaOH 용액으로 pH 를 9.5로 조정하여 침전시켰다. 부선용기에서 계면활성제인 0.3% sodium oleate 용액 1.0 ml 가하고 다공성(porosity No.4) 유리판을 통하여 질소기체를 통과시켜 침전들을 용액 표면으로 띄웠다. 부선된 침전들을 모아서 거르고 씻은 다음 8.0M HNO$_3$으로 녹여 탈이온수로 10.0ml되게 만들었다. 원자흡광도를 측정하여 농축된 원소들을 정량하였다. 동해안 강릉지역과 서해안 강화도지역의 해수 중 상기 분석원소들의 농도는 이 방법의 검출한계 이하였다. 그러나 이 방법의 응용성을 보기 위하여 해수시료에 일정량의 원소들을 첨가하여 분석한 회수율이 92% 이상이었다.

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4-비닐시클로헥센을 이용한 에틸벤젠의 제조 (Production of Ethylbenzene from 4-Vinylcyclohexene)

  • 주영제;원정임;김창민;박광천;이상옥;김홍석
    • 공업화학
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    • 제7권2호
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    • pp.326-333
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    • 1996
  • 1,3-부타디엔의 이량체인 4-비닐시클로헥센(4-vinylcyclohexene; 4-VCH)을 불균일계 촉매인 활성탄에 지지된 팔라듐과 수소주개 용매인 알콜 또는 물과 함께 니트로화합물류, 과산화수소, 염소산계[NaCln (n=1~4)], 산도등과 같은 산화제를 사용하는 촉매 수소전달반응을 응용하여 탈수소화시켜 에틸벤젠을 제조하였다. 반응온도는 $70{\sim}110^{\circ}C$, 4-VCH와 니트로화합물(니트로기가 한개 또는 두개 있는 지방족 또는 방향족 화합물)의 몰비는 1:0.02에서 1:0.5로, 4-VCH와 과산화수소, 염소산계의 몰비는 1:0.1에서 1:3을 사용하였다.

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원발 혹은 재발성 비소세포 폐암 환자에서 사이버나이프률 이용한 체부 방사선 수술의 치료 결과 (Treatment Results of CyberKnife Radiosurgery for Patients with Primary or Recurrent Non-Small Cell Lung Cancer)

  • 김우철;김헌정;박정훈;허현도;최상현
    • Radiation Oncology Journal
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    • 제29권1호
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    • pp.28-35
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    • 2011
  • 목 적: 초기 비소세포성 폐암 환자에서 수술적 절제 이외의 국소 치료로 최근 방사선 수술의 사용이 늘고 있다. 이에 저자들은 초기 혹은 재발한 비소세포성 폐암 환자를 대상으로 시행한 체부 방사선 수술의 치료 결과를 분석하여 그 유용성을 알아 보고하고자 한다. 대상 및 방법: 비소세포성 폐 종양에 대하여 방사선 수술이 시행되었던 24명의 환자, 28 lesion에 대하여 후향적 분석을 시행하였다. 이 중 원발성 종양은 19명 재발한 환자는 5명이었고 재발한 환자 5명 중 3명이 이전 치료 부위에서 재발한 환자 이었다. 원발성 종양 19명 중에서 4명은 외부 방사선 치료 후 추가로 방사선 수술을 시행 받았다. 24명의 초기 병기는 IA, IB, IIA, IIB, IIIA, IIIB, IV가 각각 7, 3, 2, 2, 3, 1, 6명이었고, 방사선 수술 당시의 T 병기는 T1 lesion이 13곳, T2가 12곳, T3가 3곳이었다. 방사선 수술은 6 MV X-ray를 이용하였고 planning target volume 1 (PTV1)에 총 방사선량 15~60 Gy(median, 50 Gy)를 3회 혹은 5회에 걸쳐 처방하여 시행하였다. 중앙 추적관찰기간은 469일이었다. 결 과: 28곳의 GTV는 0.7~108.7 mL (median, 22.9 m L)이었고, PTV1 은 5.3~184.8 mL (median, 65.4 m L)이었다. 3개월 반응률은 complete response (CR) 14곳, partial response (PR) 11곳, stable disease (SD) 3곳이었고, 마지막 추적에서의 치료반응은 CR 13곳, PR 9곳, SD 2곳, progressive disease (PD) 4곳이었다. 원발종양으로 초기 병기 IA, IB 10명에서는 50일만에 1명이 폐렴으로 사망하였고 1명이 국소재발 하였으나 나머지 환자는 6개월에서 2년간 국소재발 없이 추적관찰 되고 있으며, IIA-IIB 환자는 4명으로 환자 수가 적어서 뚜렷한 결론을 내리기 어려웠고, 재발성 폐암 환자 5명을 포함하는 10명의 IIIA-IV 병기에서는 사망 3명, 국소재발 1명, loco-regional failure 1명, regional failure 2명으로 좋지 않은 치료 결과를 보였다. 이 중에서 방사선 수술을 시행한 장소에서 재발한 경우는 총 28 1esion 중 4곳으로 85.8%의 국소제어율을 보였다. 방사선치료 양은 biologically equivalent dose (BEd) 100 $Gy_{10}$ 이하인 8 lesion 중에서 3 lesion에서 국소 재발하여 100 $Gy_{10}$ 이상인 20 lesion 중에서는 1 lesion에서만 재발한 경우보다 나빴다. 또한 중앙부의 종양과 방사선수술 당시의 병기가 T2 이상인 경우가 재발이 많았다. 결 론: 비소세포성 폐암환자에서 사이버나이프를 이용한 체부 방사선 수술은 부작용이 적으면서 높은 국소제어율을 얻을 수 있는 치료이며, 주변부의 T1 병기의 폐암에 대해서 BED 100 $Gy_{10}$ 이상의 방사선 치료가 국소제어율을 높이는데 도움이 된다고생각된다.

Up-regulation of Aldo-keto Reductase 1C3 Expression in Sulforaphane-treated MCF-7 Breast Cancer Cells

  • Lee, Sang-Han
    • Food Science and Biotechnology
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    • 제17권5호
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    • pp.1079-1085
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    • 2008
  • The chemopreventive activity of sulforaphane (SFN) occurs through its inhibition of carcinogen-activating enzymes and its induction of detoxification enzymes. However, the exact mechanisms by which SFN exerts its anti-carcinogenic effects are not fully understood. Therefore, the mechanisms underlying the cytoprotective effects of SFN were examined in MCF-7 breast cancer cells. Exposure of cells to SFN (10 ${\mu}M$) induced a transcriptional change in the AKR1C3 gene, which is one of aldo-keto reductases (AKRs) family that is associated with detoxification and antioxidant response. Further analysis revealed that SFN elicited a dose- and time-dependent increase in the expression of both the NRF2 and AKR1C3 proteins. Moreover, this up-regulation of AKR1C3 was inhibited by pretreatment with antioxidant, N-acetyl-L-cysteine (NAC), which suggests that the up-regulation of AKR1C3 expression induced by SFN involves reactive oxygen species (ROS) signaling. Furthermore, pretreatment of cells with LY294002, a pharmacologic inhibitor of phosphatidylinositol 3-kinase (PI3K), suppressed the SFN-augmented Nrf2 activation and AKR1C3 expression; however, inhibition of PKC or MEK1/2 signaling with $G\ddot{o}6976$ or PD98059, respectively, did not alter SFN-induced AKR1C3 expression. Collectively, these data suggest that SFN can modulate the expression of the AKR1C3 in MCF-7 cells by activation of PI3K via the generation of ROS.

Impact of Various Tumor Markers in Prognosis of Gastric Cancer -A Hospital Based Study from Tertiary Care Hospital of Kathmandu Valley

  • Mittal, Ankush;Gupta, Satrudhan Pd.;Jha, Dipendra Kumar;Sathian, Brijesh;Poudel, Bibek
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.1965-1967
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    • 2013
  • Background: To obtain the maximum additional information about the prognosis of gastric cancer, we compared CA-50 with other previously defined markers. Materials and Methods: This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between $1^{st}$ July 2012 and $31^{st}$ December 2012. The variables collected were age, gender, AFP, CEA, CA19-9, and CA50, assayed with ELISA reader for all cases. The cut off values for serum AFP, CEA, CA19-9, and CA-50 were 10 ${\mu}g/l$, 10 ${\mu}g/l$, 37 U/ml, and 20 U/ml, respectively according to the manufacturer's instructions. Approval for the study was obtained from the institutional research ethical committee. Results: Of the 40 examined patients, 13 patients had tumors located in the upper third of the stomach, 6 patients had tumors in the middle third, 16 patients had tumors in the lower third, and 5 patients had tumors occupying two-thirds of the stomach or more. The distribution of lymph node staging of the patients was as follows: 7 patients belonged to N0, 9 patients to N1 stage, 10 patients to N2 stage, and 14 patients to N3 stage. The statistical method of Cox proportional hazards using multivariate analysis also illustrated that tumor markers including CEA (2.802), CA19-9 (2.690), CA50 (2.101), were independent prognostic factors, as tumor size (1.603), and lymph node stage (1.614). Conclusions: The tumour markers now available, like CEA, CA 19-9 and CA 50, chiefly perceive advanced gastric cancer. The preoperative rise in those tumour marker level have a prognostic significance and may be clinically helpful in choosing patients for adjuvant management.

Anti-inflammatory Effect of LFR on LPS-stimulated THP-1 Cells

  • ;;;;정승기
    • 대한한방내과학회지
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    • 제30권2호
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    • pp.388-398
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    • 2009
  • Background and Objective: Luffae Fructus Retinervus (LFR) is used for investigating symptoms of inflammation. We have evaluated the anti-inflammatory effect of LFR by analyzing the expression of pro-inflammatory cytokines. Materials and Methods : We differentiated THP-l cells into macrophage-like cells by treatment with PMA. Inflammation was induced by treatment with LPS and PMA. We determined the safe concentration of LFR by using the MTS and MTT assays and using PD 98059 as a negative control for comparison of the anti-inflammatory effect of LFR. Results : The MTS and MTT analysis showed that the cell survival rate was >80% within the LFR concentration range of 10-100 ng/ml and began to decrease to >80% at 1 ${\mu}g/ml$. By RT-PCR analysis, the gene expression of TNF-${\alpha}$, IL-8, TGF-${\beta}$, IL-6, IL-${\beta}$1, and IL-10 levels were down-regulated when monocyte-derived macrophages were treated with concentrations of LFR between 10 ng/mL and 100 ng/mL. Conclusion : We conclude that LFR exerts an anti-inflammatory effect by inhibiting the expression of pro-inflammatory activity. The results suggest a promising way to treat general inflammatory diseases.

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