• Title/Summary/Keyword: Dose Rate

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In vitro Study of the Antagonistic Effect of Low-dose Liquiritigenin on Gemcitabine-induced Capillary Leak Syndrome in Pancreatic Adenocarcinoma via Inhibiting ROS-Mediated Signalling Pathways

  • Wu, Wei;Xia, Qing;Luo, Rui-Jie;Lin, Zi-Qi;Xue, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4369-4376
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    • 2015
  • Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma.

Survival Rate, Growth and NP Accumulation of the Striped Bitterling, Acheilognathus yamatsutae Long-term Exposed to Nonylphenol (NP) (노닐페놀 (NP)에 장기간 노출된 줄납자루, Acheilognathus yamatsutae의 NP 체내 축적, 성장 및 생존율)

  • Jin, Young-Guk;Kim, Chi-Hong;Lee, Chul-Woo;Lee, Jung-Sick
    • Journal of fish pathology
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    • v.21 no.1
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    • pp.57-66
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    • 2008
  • Striped bitterling, Acheilognathus yamatsutae (TL: 4.25 ㎝, TW: 0.73 g)were exposed to 0.3, 1.3, 17.6 and 33.7 ㎍ L-1 (nominal concentrations) of nonylphenol (NP) for a period of 20 weeks. We studied on accumulation, growth and survival rate. After 20 weeks of exposure, the accumulation of NP in the body of the female and male was increased with increasing dose-dependent and female was higher than male. 4 weeks of exposure, TL of female striped bitterling was found to be increased in all of the dose group compared to control and 12 weeks of exposure, similar or some decreased in all of the dose group compared to control. 20 weeks of exposure, increased in all of the dose group compared to control and TL at 33.7 ㎍ NP L-1 were significantly higher than those in control (p <0.05). 4 weeks of exposure, TL and TW of male striped bitterling was found to be increased in all of the dose group compared to control and significantly higher in TL of 33.7 ㎍ NP L-1 (p <0.05). 12 and 20 weeks of exposure, TL and TW decreased in all of the dose group compared to control and significantly lower in 1.3 ㎍ NP L-1 of 12 weeks. Survival rate in both groups decreased with increasing NP concentration and there was a significant difference between control group and experimental groups exposed to each NP concentration.

Effects of low dose gamma irradiation on the germination and physiological activity of old red pepper ( Capsicum annuum L.) seed (묵은 고추종자의 발아와 생리활성에 미치는 저선량 방사선조사 효과)

  • Kim, Jae-Sung;Back, Myung-Hwa;Lee, Hae-Youn;Lee, Young-Keun
    • Journal of Radiation Protection and Research
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    • v.26 no.4
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    • pp.409-415
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    • 2001
  • To observe the stimulating effects of low dose gamma radiation on the germination and physiological activity of germinating seeds of old red pepper (Capsicum annuum L. cv Jokwang and cv. Hongkwang), seeds were irradiated at the dose of $2{\sim}50 Gy$. The germination rate of irradiation group was higher than that of the control. Especially it was highest at the early stage of induction. The germination rate at 7 days after sowing in Jokwang and Hongkwang cultivar was high as 74% and 11% at 4 Gy and 8 Gy irradiation group, respectively. The seedling height of Jokwang cultivar was noticeably high at 4 Gy irradiation group and that of Hongkwang cultivar at 8 Gy irradiation group. The protein contents of seedlings from seeds irradiated with low dose gamma radiation of Jokwang cultivar increased at the late stage of induction and that of Hongkwang cultivar at the early stage of induction. Catalase and peroxidase activities of seedlings from seeds irradiated with low dose gamma radiation of Jokwang cultivar increased at 4 Gy irradiation group and that of Hongkwang cultivar at 8 Gy irradiation group.

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Biological Effects of Different Chronic Medium-Dose-Rate Gamma Radiation Period Exposed on Mice (장기 중선량률의 감마선 피폭 기간에 따른 실험동물의 생물학적 영향 연구)

  • Kim, Jae-Kyung;Jin, Yeung Bae;Oh, Su-Mi;Lee, Yun-Jong;Sung, Nak-Yun;Song, Beom-Seok;Park, Jong-Heum;Byun, Eui-Baek;Lee, Ju-Woon;Kim, Jae-Hun
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.135-139
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    • 2013
  • Recently, chronic gamma radiation exposure on biological effects in middle dose-rates have become a serious concern. We investigated the biological effects of middle dose chronic exposure to gamma ray. Fifty male 6-week-old specific free Balb/c mice were randomly divided into five groups (four groups irradiated and one non-irradiated control group). Gamma radiation exposed in Gamma phytotron on Advanced Radiation Technology Institute (Jeongeup, Korea). Irradiation was carried out for 1 or 2 weeks using gamma rays at dose rates of 45 and $50mGy\;h^{-1}$ with total doses 7.56 Gy ($45mGy\;h^{-1}$, 1 week), 8.4 Gy ($50mGy\;h^{-1}$, 1 week), 15.12 Gy ($45mGy\;h^{-1}$, 2 weeks) and 16.8 Gy ($50mGy\;h^{-1}$, 2 weeks). After irradiation, immediately we sacrificed and counted body and organ weights. Moreover we counted spleen cell numbers. Compared with control non-irradiated group, all irradiated groups of body and spleen weights showed significant decreased. However, no significant alteration was observed between same irradiated period groups. In spleen cell numbers, reduced compared to the control group. However, significant alteration was observed between same irradiated period groups ($45mGy\;h^{-1}$, $50mGy\;h^{-1}$). These results demonstrated biological effects according to the radiation dose rate and irradiated period.

The Comparison of Clinical Outcomes between GnRH Agonist Long Protocol and GnRH Antagonist Short Protocol in Oocyte Donation Cycles (난자공여를 통한 체외수정 시술에서 성선자극호르몬 유리호르몬 효능제 장기요법과 길항제 단기요법 사이의 임상 결과 비교)

  • Rhee, Jeong-Ho;Park, Joon-Chul;Kim, Jong-In
    • Clinical and Experimental Reproductive Medicine
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    • v.30 no.1
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    • pp.95-103
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    • 2003
  • Objective : To assess and compare the clinical outcomes between GnRH agonist long protocol and GnRH antagonist short protocol in oocyte donation program. Materials and Methods: Of total 18 oocyte donation cycles, controlled ovarian hyperstimulation (COH) were performed with GnRH agonist long protocol and GnRH antagonist short protocol in initial 9 cycles and later 9 cycles, respectively. Oral estradiol valerate and progesterone in oil we re administrated to all recipients for endometrial preparation. Oral estradiol administration was started from donor cycle day 1 after full shut down of gonadal axis with GnRH agonist in patients with ovarian function. Progesterone was injected from oocyte retrieval day of donor initially, then continuously till pregnancy 12 weeks if pregnancy was ongoing. We compared the parameters of clinical outcomes, such as number of the retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, COH duration, total gonadotropin dose for COH between GnRH agonist long protocol group and GnRH antagonist group. Statistical analysis was performed using Mann-Whitney test, p<0.05 was considered as statistically significant. Results: The number of retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate were $14.89{\pm}7.83$, 81%, 64%, 78%, 31%, 78%, respectively in GnRHa long protocol group and $11.22{\pm}8.50$, 79%, 64%, 67%, 34%, 56%, respectively in GnRH antagonist group. There was no significant differences in parameters of clinical outcomes between 2 groups (all p value >0.05). Duration and total gonadotropin dose for COH were $10.94{\pm}1.70$ days and $43.78{\pm}6.8$ vials in 18 cycles, $12.00{\pm}1.73$ days and $48.00{\pm}6.93$ vials in agonist group, $9.88{\pm}0.78$ days and $39.55{\pm}3.13$ vials in antagonist group, respectively. In GnRH agonist long protocol group, significantly longer duration and higher gonadotropin dose for COH were needed (p=0.012). Conclusion: In oocyte donation program, clinical outcomes from controlled ovarian hyperstimulation with GnRH antagonist were comparable to those from GnRH agonist long protocol group, so controlled ovarian hyperstimulation with GnRH antagonist may be effective as GnRH agonist long protocol. At least there may not be harmful effects of GnRH antagonist on oocyte development and quality.

The Clinical Study on the Effects of $Tapazole^{(R)}\;upon\;^{131}I$ Uptake in Hyperthyroidism (갑상선(甲狀腺) 기능항진증(機能亢進症)에서 $Tapazole^{(R)}$$^{131}I$섭취율(攝取率)에 미치는 영향(影響)에 관(關)한 임상적(臨床的) 고찰(考察))

  • Ro, Heung-Kyu;Lee, Jung-Sang;Koh, Chang-Soon;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.3 no.2
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    • pp.17-22
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    • 1969
  • The differences in the change of the uptake rate of radioactive iodine ($^{131}I$) in the thyroid gland after $Tapazole^{(R)}$ administration before $^{131}I$ treatment were analysed in 137 patients who were diagnosed as diffuse toxic goiter in the Radioisotope Clinic and Laboratory, Seoul National University Hospital since Jan. 1967 to July, 1969. The uptake rate of the therapeutic dose of $^{131}I$ was changed diffusely compared with that of the trace dose in the patients who had no $Tapazole^{(R)}$ administration before $^{131}I$ treatment. In those patients who had $Tapazole^{(R)}$ more than 20 mg/day for more than one week before $^{131}I$ treatment, the uptake rate was decreased significantly. When the patients discontinued the administration of $Tapazole^{(R)}$ 7 days prior to $^{131}I$ treatment, the uptake rate was increased in all cases.

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In Vivo Antitumor Efficacy of Cw252053, A Folate-based Thymidylate Synthase Inhibitor

  • Oh, Se-Woong;Ha, Jong-Ryul;Baek, Du-Jong
    • Archives of Pharmacal Research
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    • v.24 no.4
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    • pp.323-326
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    • 2001
  • Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

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Effect of Gonadotropin-releasing Hormone Administration in Repeat-breeder Hanwoo (저수태 한우에 대한 성선자극 호르몬 방출호르몬 투여 효과)

  • 임석기;우재석;윤상보;전기준
    • Journal of Embryo Transfer
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    • v.12 no.1
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    • pp.117-122
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    • 1997
  • The objective of this study was to enhance the pregnancy rate of repeat-breeder Hanwoo with gonadotropin-releasing hormone(Gn-RH) at the time, dose and site of administration.The results obtained were summaried as fallows:1.Ovulation time and pregnancy rate following GnRH administration time was 46.0, 27.4, 42.0 and 43.2hr and 33.3, 57.1, 37.5 and 40.0% at non-treatment, estus, 1st A' and 2nd Al treatment, respectively.2. Ovulation in repeat-breeder was induced 100% within 24hr with GnRH administration at the time of estrus.3. Ovulation time and pregnancy rate following GnRH adminstration dose and site was 25.2, 32.6, 17.6 and 27.6hr, and 28.6, 42.9, 75.0 and 66.7% at 50$\mu$g+IU, 50$\mu$g+IM, 100$\mu$g+IU and 100$\mu$g+IM treatments, respectively. It is concluded that GnRH administration for repeat-breeder was enhanced the pregnancy rate when treated with 100$\mu$g intrauterine at the time of estrus.

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Intermittent Administration of Parathyroid Hormone for Orthodontic Tooth Movement in Mongrel Dogs: Preliminary Study

  • Won-Ho Kim;Bo Ram Lee;Hey-Yun Kim;Minji Kim;Jin-Woo Kim
    • Journal of Korean Dental Science
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    • v.16 no.2
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    • pp.182-191
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    • 2023
  • Purpose: This study investigated the orthodontic tooth movement after weekly parathyroid hormone (PTH) injection in mongrel dogs and analyzes bone formation activity on the tension and pressure sides of the tooth movement in mongrel dogs. Materials and Methods: Three mongrel dogs were used in this study. The first premolar was extracted and orthodontic force using 150 g of closed coil springs between the canine and second premolar was applied. The low-dose PTH group (PTH_1) and high-dose PTH group (PTH_2) received weekly injections of 1.61 ㎍/kg and 3.23 ㎍/kg of PTH, respectively. The control group received weekly injections of 1 ml of saline. Clinical, histomorphometric analysis were carried out. Result: The orthodontic tooth movement was greatest in the PTH_2 group and the lowest in the control group. Fluorescence staining images showed higher bone remodeling on the tension side of the tooth movement in the PTH_1 and PTH_2 groups. PTH_2 group showed a thicker labeling band than the PTH_1 group. PTH_2 group showed the highest mineral apposition rate and bone formation rate, followed by the PTH_1 group and the control group. Conclusion: Weekly intermittent PTH injection, especially in the short-term and at higher doses with orthodontic force, successfully increased orthodontic tooth movement and bone remodeling in mongrel dogs.

Flavonoids of Rosa roxburghii Tratt Act as Radioprotectors

  • Xu, Ping;Zhang, Wen-Bo;Cai, Xin-Hua;Lu, Dan-Dan;He, Xiao-Yang;Qiu, Pei-Yong;Wu, Jiao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8171-8175
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    • 2014
  • Background: To study the radioprotective effects of flavonoids from Rosa roxburghii Tratt (FRT). Materials and Methods: The radioprotective effects of FRT were investigated by examining cell viability, 30-day survival of mice and the number of colony-forming units in spleen (CFU-S) after total-body 60Co irradiation. Results: The survival rates of irradiated cells gradually increased with increasing concentrations of FRT. The survival rate was the highest at 87% with a concentration of $30{\mu}g/mL$. Pretreatment with FRT was needed to realize its radioprotective activity in mice at the dose of 60 mg/kg. With the increasing doses of 30 mg/kg, 60 mg/kg and 120 mg/kg, the numbers of CFU-S increased, and were significantly different compared with the control group. Conclusions: Pretreatment with FRT prior to irradiation resulted in significantly higher cell survival at 24 h after 5 Gy radiation, increased 30-day survival in mice after exposure to a potentially lethal dose of 8 Gy, and resulted in a higher number of CFU-S in mice after exposure to a dose of 6 Gy. These results collectively indicate that FRT is an effective radioprotective agent.