• Title/Summary/Keyword: Dose-response

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Vasodilation Effect of the Water Extract of Rheum palmatum L. in Rat Thoracic Aorta.

  • Koo, Bon-Sik;Kim, Hong-Yeoul;Park, Seong-Kyu
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.203-203
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    • 2002
  • Rheum palmatum L. has been used for treatment of hypertension, lipemia, and paramenia in the oriental gerbal medicines for a long time. We have examined the relaxational response to the water extract of Rheum palmaum L. in isolated thoracic aorta from sprague dawley (SD) rat in the presence and absence of endothelium. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to Rhizoma Rhei were investigated in vessels precontracted with 5-hydroxytryptamine. We found that the ghoracic aorta segments responded to the water extract of Rheum palmatum L. (ERP) with a dose-dependent vasorelaxation. We found that 1.The thoracic aorta sehments responded to ERP with a dose-dependent vasodiliation. 2.The 5-HT induced contraction at 10$\^$-4/M were inhibited by 85.8% after addition of the 0.1 g/mL water extract of ERP. 3. The 5-HT induced contraction at 10$\^$-4/ M with and without endothelium were inhibited by 86.4% and 85.8% after addition of the 0.1g/mL ERP. 4. After pre-treatment of the thoracic aorta with 10$\^$-4/M N$\^$G/-monomethyl-L-arginine(L-NMMA), inducible niric oxide synthase inhibitor, the vessels has not response to the contraction. In conclusion, ERP induced reaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. and it has potent vasodilation.

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Effect of Prostaglandins $D_2,\;E_2\;and\;I_2\;on\;the\;Regulation\;of\;K_{ATP}$ Channel Activity in Rat Cardiac Myocytes

  • Ju, Jeong-Min;Nah, Seung-Yeol;Kim, Jae-Ha
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.5
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    • pp.507-512
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    • 1999
  • Contribution of prostaglandins $D_2,\;E_2\;and\;I_2\;(PGD_2,\;PGE_2\;and\;PGI_2)$ on the regulation of ATP-sensitive $K^+$ channel $(K_{ATP}\;channel)$ was investigated in isolated single rat ventricular cardiac myocytes using the patch clamp technique. $PGD_2,\;PGE_2\;and\; PGI_2$ did not affect $K_{ATP}$ channel activity in the inside-out patch, but increased channel activity in a dose-dependent manner when the channel activities were attenuated by the administration of 100 ${\mu}M$ ATP to the internal solution in the inside-out patch. Channel activations by the prostaglandins were abolished by 50 ${\mu}M$ glibenclamide, a $K_{ATP}$ channel blocker. Dose-response curves of relative channel activity against the ATP concentrations of internal solution in the inside-out patch were shifted to the right in the presence of those three prostaglandins. The rank order of the channel stimulatory potencies $(as\;IC_{50}\;for\;ATP)$ calculated from the dose-response curves were $PGI_2\;>\;PGD_2\;>\;PGE_2.$ Conductance of the channel was not changed by those three prostaglandins. In conclusion, we suggest that prostaglandins $D_2,\;E_2\;and\;I_2$ are involved in the regulation of $K_{ATP}$ channel activity in certain circumstances, and that those three prostaglandins may cause myocardial relaxation by opening $K_{ATP}$ channels, thus protecting the heart from ischema.

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Treatment results of radiotherapy following CHOP or R-CHOP in limited-stage head-and-neck diffuse large B-cell lymphoma: a single institutional experience

  • Jeong, Jae-Uk;Chung, Woong-Ki;Nam, Taek-Keun;Yang, Deok-Hwan;Ahn, Sung-Ja;Song, Ju-Young;Yoon, Mee Sun;Kim, Yong-Hyeob
    • Radiation Oncology Journal
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    • v.35 no.4
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    • pp.317-324
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    • 2017
  • Purpose: This study evaluated outcomes of radiotherapy (RT) after chemotherapy in limited-stage head-and-neck diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Eighty patients who were treated for limited-stage head-and-neck DLBCL with CHOP (n = 43) or R-CHOP (n = 37), were analyzed. After chemotherapy, RT was administered to the extended field (n = 60) or the involved field (n = 16), or the involved site (n = 4). The median dose of RT ranged from 36 Gy in case of those with a complete response, to 45-60 Gy in those with a partial response. Results: In all patients, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 83.9% and 80.1%, respectively. In comparison with the CHOP regimen, the R-CHOP regimen showed a better 5-year DFS (86.5% vs. 73.9%, p = 0.027) and a lower rate of treatment failures (25.6% vs. 8.1%, p = 0.040). The volume (p = 0.047) and dose of RT (p < 0.001) were significantly reduced in patients treated with R-CHOP compared to that in those treated with CHOP. Conclusion: The outcomes of RT after chemotherapy with R-CHOP were better than those of CHOP regimen for limited-stage head-and-neck DLBCL. In patients treated with R-CHOP, a reduced RT dose and volume might be feasible without increasing treatment failures.

Analysis of gene expression profiles to study malaria vaccine dose efficacy and immune response modulation

  • Dey, Supantha;Kaur, Harpreet;Mazumder, Mohit;Brodsky, Elia
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.32.1-32.15
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    • 2022
  • Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

Treatment outcome of hepatic re-irradiation in patients with hepatocellular carcinoma

  • Seol, Seung Won;Yu, Jeong Il;Park, Hee Chul;Lim, Do Hoon;Oh, Dongryul;Noh, Jae Myoung;Cho, Won Kyung;Paik, Seung Woon
    • Radiation Oncology Journal
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    • v.33 no.4
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    • pp.276-283
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    • 2015
  • Purpose: We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma. Materials and Methods: Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for ${\alpha}/{\beta}=10Gy$ ranged from $31.25Gy_{10}$ to $93.75Gy_{10}$ (median, $44Gy_{10}$). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. Results: The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ${\geq}45Gy_{10}$ and $<45Gy_{10}$, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ${\geq}50Gy_{10}$. Conclusion: Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.

Innate immune responses of common carp, Cyprinus carpio L. against antiviral activity inducers (항바이러스 활성 유도 물질에 대한 잉어의 선천성 면역 반응)

  • Cho, Mi-Young;Kim, Su-Mi;Kim, Eun-Jeon;Shon, Sang-Gyu;Kim, Jin-Woo;Park, Soo-Il
    • Journal of fish pathology
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    • v.20 no.2
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    • pp.189-200
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    • 2007
  • To investigate the innate immune response involved in early stage of anti-viral defence, carps were injected with UV-inactivated spring viraemia of carp virus (SVCV), poly inosinic:cytidylic acid (Poly I:C) and concanavalin A (Con A), respectively and examined lysozyme activity, serum complement activity and chemiluminescent (CL) response of leucocytes isolated from head kidney at 3 days post-injection. There was no significant difference in plasma lysozyme activities among all experimental groups. However, lysozyme activities of head kidney in the groups injected with antiviral activity inducers were significantly higher than those of the control injected with physiological saline. Bactericidal activities of serum of the groups injected with antiviral activity inducers were not significantly different from control group. However, the CL responses were significantly higher at lower dose of Poly I:C and Con A, whilst dose-dependent increase was shown in UV-inactivated SVCV-injected group. In the challenge test with 1×104 TCID50/fish of SVCV at 4 days post-injection, UV-inactivated SVCV- and Poly I:C-injected groups showed higher relative percent survival (RPS) than Con A-injected group. Furthermore, strong protection was observed in the group injected higher dose of Poly I:C although showed lower activities in lysozyme and CL response. These results suggested that Poly I:C might stimulate other factors belonging to non-specific immune system have induced protective immunity against the SVCV challenged.

Study on Dosimetric Properties of Radiophotoluminescent Glass Rod Detector (유리선량계의 선량 특성에 관한 연구)

  • Rah, Jeong-Eun;Shin, Dong-Oh;Hong, Ju-Young;Kim, Hee-Sun;Lim, Chun-Il;Jeong, Hee-Gyo;Suh, Tea-Suk
    • Journal of Radiation Protection and Research
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    • v.31 no.4
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    • pp.181-186
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    • 2006
  • A radiophotoluminescent glass rod detector (GRD) system has recently become commercially available. We investigate the dosimetric properties of the GRD regarding the reproducibility of signal, dose linearity and energy dependence. The reproducibility of five measurements for 50 GRDs is presented by an average of one standard deviation of each GRD and it is ${\pm}1.2%$. It is found to be linear in response to doses of $^{60}Co$ beam in the range 0.5 to 50 Gy with a coefficient of linearity of 0.9998. The energy dependence of the GRD is determined by comparing the dose obtained using cylindrical chamber to that by using the GRD. The GRD response for each beam is normalized to the response for a $^{60}Co$ beam. The responses for 6 and 15 MV x-ray beams are within ${\pm}1.5%$ (1SD). The energy response of GRD for high-energy photon is almost the same as the energy dependence of LiF:Mg:Ti (TLD-100)and shows little energy dependence unlike p-type silicon diode detector. The GRDs have advantages over other detectors such diode detector, and TLD: linearity, reproducibility and energy dependency. It has been verified to be an effective device for small field dosimetry for stereotactic radiosurgery.

Induction of Radiation Adaptive Response in Lymphocytes of patients Undergoing Bone Scintigraphy (골 신티그라피를 시행한 환자의 림프구에서 방사선 적응반응의 유도에 관한 연구)

  • Min, Jung-Jun;Bom, Hee-Seung
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.2
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    • pp.172-177
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    • 1999
  • Purpose: The purpose of this study was to ascertain whether radiation adaptive response could be induced by Tc-99m-methylene diphosphonate (Tc-99m-MDP) in peripheral lymphocytes of patients undergoing bone scintigraphy. Materials and Methods: Lymphocytes from 22 patients (6 males, 16 females, mean age $50{\pm}14$ years) were collected before and after bone scintigraphy using 740 MBq Tc-99m-MDP Lymphocytes from 10 controls (6 males, 4 females, mean age $43{\pm}7$ years) were also collected. They were exposed to challenge dose of 2 Gy gamma rays using a cell irradiator. Number of ring-form and dicentric chromosomes per 600 cells (chromosomal aberrations) was counted under the light microscope. Results: Chromosomal aberrations in patients before bone scintigraphy ($385.1{\pm}30.5$) was not different from that of controls ($367.8{\pm}36.6$). However, chromosomal aberrations in patients after bone scintigraphy was significantly decreased to $192.6{\pm}22.1$ (p=0.0001). Conclusion: Low dose gamma-irradiation by Tc-99m-MDP used for bone scintigraphy induces a cytogenetic adaptive response in peripheral lymphocytes.

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The Role of Radiation Therapy in the Unresectable Rectal Cancers (절제 불가능 직장암에서 방사선 치료의 역할)

  • Kim, Woo-Cheol;Seong, Jin-Sil;Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.173-180
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    • 1995
  • Purpose: Unresectable rectal cancer has a grave prognosis. regardless of the therapy used and median survival is less than 1 rear. Also, it is reported by many authors that $50-80\%$ of unresectable lesions were rendered resectable by radiation therapy and the median survival time for the completely resected patients were better than that of the unresected patients. So we analyzed retrospectively our data for the better treatment outcome in these patients. Materials and MEthods:From 1980 to 1992, 45 patients with initially unresectable tumors in the rectum were treated with radiation therapy with/without surgery in Department of Radiation Oncology, Yonsei Cancer Center 10 MV radiation and multiple field technique (box or AP/PA) were used. The total dose was 28-70 Gy and median dose was 48 Gy. We evaluated the lesion status at 45-50 Gy for operability. If the lesions appeared to be resectable, the Patients were operated on 4-6 weeks after radiation therapy. But if the lesions were still fixed, the radiation dose was increased to 60-65 Gy. Results: For all patients, the 2-year actuarial survival was $13.3\%$ and median survival was 9.5 months. Of 6 patients who had received less than 45 Gy, only $17\%$ of patients responded, but in the patients who had received more than 45 Gy, $60\%$ of response rate was achieved Six of the 24 patients$(25\%)$ underwent surgical resections following RT. For patients undergoing curative resection. the two-rear survival was $50\%,$ but that of the patients without resection was $9.5\%$ (p<0.01). Survival of patients with complete response following RT was $50\%$ at 2 years. Survival of patients with partial response, stable disease and progressive disease after RT was $13.4\%,\;15.4\%,\;0\%$ respectively (P<0.05). Conclision: Our data suffests that the efforts which can increase the response rate and aggressive surgical approach are needed to achieve the better local control and survival in unresectable rectal cancers.

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Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: preliminary results of a randomized controlled trial

  • Aghili, Mahdi;Khalili, Nastaran;Khalili, Neda;Babaei, Mohammad;Farhan, Farshid;Haddad, Peiman;Salarvand, Samaneh;Keshvari, Amir;Fazeli, Mohammad Sadegh;Mohammadi, Negin;Ghalehtaki, Reza
    • Radiation Oncology Journal
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    • v.38 no.2
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    • pp.119-128
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    • 2020
  • Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/㎡ from day 1-5 twice daily and oxaliplatin 50 mg/㎡ on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/㎡ twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.