• 제목/요약/키워드: Dose-response

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작업장에서 취급하는 CMR물질의 용량반응평가 방법 비교 (A Comparison of Dose-Response Assessments for CMR Materials in the Workplace)

  • 이경화;최한영;김치년;노영만;최희진;박채리
    • 한국산업보건학회지
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    • 제28권1호
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    • pp.51-60
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    • 2018
  • Objectives: Currently, there is only limited knowledge regarding the hazard of low-level exposure to CMR materials in workplaces. To overcome this limitation, a reference concentration for workers($RfC_w$) from among the risk assessment tools proposed by the US EPA is widely used to set a provisional workplace exposure level(PWEL) for CMR materials for which there are no established Korea Occupational Exposure Limits(KOELs) or subjective chemicals for work environment measurements as regulated by Korea Ministry of Employment and Labor(KMOEL). A simple European calculator of derived no effect level(SECO-DNEL) as proposed by REACH can also be used in place of $RfC_w$ to set the PWEL for chemicals. This study was performed to test the acceptability of using SECO-DNEL as an alternative to $RfC_w$ when setting a PWEL for low-level exposures. Methods: The $RfC_w$ and DNEL for the five CMR materials of dinitrogen oxide, catechol, 2-phenoxy ethanol, carbitol, and carbon black were calculated using the dose-response assessments of the US EPA for $RfC_w$ and REACH guidance for SECO-DNEL, respectively. They were compared using paired t-tests to determine the statistical differences between them. Results: For the five chemicals, the $RfC_w$ were 2.53 ppm, 0.10 ppm, 1.73 ppm, 1.66 ppm, and $0.05mg/m^3$, respectively, while the SECO-DNEL were 2.01 ppm, 0.11 ppm, 1.83 ppm, 1.77 ppm, $0.14mg/m^3$, respectively. There was no statistically significant difference between $RfC_w$ and SECO-DNEL. Conclusions: This study suggests that the SECO-DNEL could be applied in place of $RfC_w$ to set a PWEL for low-level exposure to chemicals, especially CMR materials. To further ensure the reliability of SECO-DNEL as an alternative tool, more chemicals should be applied for calculation and comparison with $RfC_w$.

Glucose Tolerance and Insulin Response to Intravenous Glucose Load in Sheep Fed on Germinated Sorghum Grain

  • Achmadi, Joelal;Pangestu, Eko;Wahyono, Fajar
    • Asian-Australasian Journal of Animal Sciences
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    • 제20권10호
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    • pp.1575-1579
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    • 2007
  • The glucose tolerance and pancreatic insulin secretion response to glucose in sheep fed on germinated sorghum grain were determined using an intravenous glucose load. Twelve male Thin Tail sheep (an Indonesian native sheep, 12 months old and 14.8 kg average body weight) were divided randomly into sorghum grain-based (S), germinated sorghum grain-based (G) and maize grain-based (C) diets. Sheep were maintained at the same daily intake levels of metabolizable energy and crude protein in the diets throughout the experimental period. After two months of the experimental conditions, each diet group was subjected to an intravenous glucose load experiment in which five doses of glucose (0, 10, 20, 40 and 80 mg/kg BW) were injected to estimate the rate of glucose removal from blood and the pancreatic insulin secretion response. For each sheep and each glucose load dose, the incremental blood serum glucose and insulin concentrations above pre-injection concentration were calculated as serum glucose and insulin response areas. At all glucose doses, sheep fed on S diet had a greater (p<0.05) glucose response area compared to those of sheep fed on G and C diets. Likewise at all glucose doses, the insulin response area was smaller (p<0.05) in sheep fed on S diet than in sheep fed on G and C diets. The glucose and insulin response areas in sheep fed on G and C diets differed slightly. It was concluded that the portion of maize grain in the ruminant ration could be substituted by germinated sorghum grain.

Clinical application of anti-M$\ddot{u}$llerian hormone as a predictor of controlled ovarian hyperstimulation outcome

  • Lee, Jae Eun;Lee, Jung Ryeol;Jee, Byung Chul;Suh, Chang Suk;Kim, Ki Chul;Lee, Won Don;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
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    • 제39권4호
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    • pp.176-181
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    • 2012
  • Objective: In 2009 anti-M$\ddot{u}$llerian hormone (AMH) assay was approved for clinical use in Korea. This study was performed to determine the reference values of AMH for predicting ovarian response to controlled ovarian hyperstimulation (COH) using the clinical assay data. Methods: One hundred sixty-two women who underwent COH cycles were included in this study. We collected data on age, basal AMH and FSH levels, total dose of gonadotropins, stimulation duration, and numbers of oocytes retrieved and fertilized. Blood samples were obtained on cycle day 3 before gonadotropin administration started. Serum AMH levels were measured at a centralized clinical laboratory center. The correlation between the AMH level and COH outcomes and cut-off values for poor and high response after COH was analyzed. Results: Concentration of AMH was significantly correlated with the number of oocytes retrieved (OPU; r=0.700, p<0.001). The mean${\pm}$SE serum AMH levels for poor ($OPU{\leq}3$), normal ($4{\leq}OPU{\leq}19$), and high ($OPU{\geq}20$) response were $0.94{\pm}0.15$ ng/mL, $2.79{\pm}0.21$ ng/mL, and $6.94{\pm}0.90$ ng/mL, respectively. The cut-off level, sensitivity and specificity for poor and high response were 1.08 ng/mL, 85.8%, and 78.6%; and 3.57 ng/mL, 94.4%, and 83.3%, respectively. Conclusion: Our data present clinical reference values of the serum AMH level for ovarian response in Korean women. The serum AMH level could be a clinically useful predictor of ovarian response to COH.

Radicicol Inhibits iNOS Expression in Cytokine-Stimulated Pancreatic Beta Cells

  • Youn, Cha Kyung;Park, Seon Joo;Li, Mei Hong;Lee, Min Young;Lee, Kun Yeong;Cha, Man Jin;Kim, Ok Hyeun;You, Ho Jin;Chang, In Youp;Yoon, Sang Pil;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권4호
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    • pp.315-320
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    • 2013
  • Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

Immune Responses in Broiler Chicks Fed Propolis Extraction Residue-supplemented Diets

  • Eyng, C.;Murakami, A.E.;Santos, T.C.;Silveira, T.G.V.;Pedroso, R.B.;Lourenco, D.A.L.
    • Asian-Australasian Journal of Animal Sciences
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    • 제28권1호
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    • pp.135-142
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    • 2015
  • This study was conducted to evaluate the effect of inclusion of propolis extraction residue in the feed of broilers from 1 to 21 d of age on phagocytic activity of macrophages, cutaneous basophil hypersensitivity response to phytohemagglutinin, antibody production against Newcastle disease, lymphoid organ weight and hematological profile and to determine the optimal level of inclusion. 120 chicks, reared in metabolism cages until 21 days of age, were distributed in a completely randomized design, with five treatments (0%, 1%, 2%, 3%, and 4% of propolis residue) and six replications. The relative weight of thymus and monocyte percentage were affected by propolis residue, with a quadratic response (p<0.05) and lowest values estimated at 2.38% and 2.49%, respectively. Changes in relative weight of cloacal bursa and spleen, percentage of lymphocyte, heterophil, basophil, eosinophil, and heterophil:lymphocyte ratio, antibody production against Newcastle disease, phagocytic activity of macrophages and the average number of phagocytosed erythrocytes were not observed. The nitric oxide production with regard to positive control (macrophages+erythrocytes) decreased linearly (p<0.05) with increased doses of propolis residue. The remaining variables of nitric oxide production (negative control - macrophages, and difference between the controls) were not affected by propolis residue. The cutaneous basophil hypersensitivity response to phytohemagglutinin as determined by the increase in interdigital skin thickness exhibited a quadratic response (p<0.05), which predicted a lower reaction response at a dose of 2.60% of propolis residue and highest reaction response after 43.05 hours of phytohemagglutinin injection. The inclusion of 1% to 4% of propolis extraction residue in broiler diets from 1 to 21 days of age was not able to improve the immune parameters, despite the modest changes in the relative weight in thymus, blood monocyte percentage, nitric oxide concentration, and interdigital reaction to phytohemagglutinin.

Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune Response

  • Ying Nie;Dongqing Deng;Lumin Mou;Qizhou Long;Jinzhi Chen;Jiahong Wu
    • Journal of Microbiology and Biotechnology
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    • 제33권5호
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    • pp.600-606
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    • 2023
  • Dengue virus (DENV) is a widespread arbovirus. To efficiently establish infection, DENV evolves multiple strategies to hijack the host innate immune response. Herein, we examined the inhibitory effects of DENV serotype 2 (DENV2) nonstructural proteins on RIG-I-directed antiviral immune response. We found that DENV2 NS2A, NS2B, NS4A, and NS4B significantly inhibited RIG-I-mediated IFN-β promoter activation. The roles of NS2B in RIG-I-directed antiviral immune response are unknown. Our study further showed that NS2B could dose-dependently suppress RIG-I/MAVS-induced activation of IFN-β promoter. Consistently, NS2B significantly decreased RIG-I- and MAVS-induced transcription of IFNB1, ISG15, and ISG56. Mechanistically, NS2B was found to interact with MAVS and IKKε to impair RIG-I-directed antiviral response. Our findings demonstrated a previously uncharacterized function of NS2B in RIG-I-mediated antiviral response, making it a promising drug target for anti-DENV treatments.

Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma

  • Lee, Ju Hye;Kim, Dong Hyun;Ki, Yong Kan;Nam, Ji Ho;Heo, Jeong;Woo, Hyun Young;Kim, Dong Won;Kim, Won Taek
    • Radiation Oncology Journal
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    • 제32권3호
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    • pp.170-178
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    • 2014
  • Purpose: We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. Materials and Methods: We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. Results: Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). Conclusion: Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

  • Wu, Xue-Yan;Huang, Xin-En;You, Shan-Xi;Lu, Yan-Yan;Cao, Jie;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.2019-2022
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    • 2013
  • Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

제한병기 소세포폐암에서 흉부 방사선 치료의 도입 시기에 따른 치료 효과의 비교 분석 (The effects according to the timing of thoracic radiotherapy in limited stage small cell lung cancer)

  • 박상기;김근화;정성수;신경상;김애경;조해정;서지원;김재성;조문준;김주옥;김선영
    • Tuberculosis and Respiratory Diseases
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    • 제43권6호
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    • pp.903-915
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    • 1996
  • Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The liming, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks 10 the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration : Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was nor different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicities, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group (p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.

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국소성 소세포 폐암에 대한 복합화학요법 및 방사선 병용치료의 효과 (The Result of Combined Modality Treatment for Limited Stage Small Cell Lung Cancer)

  • 김재철;장양숙;류삼열;박인규
    • Radiation Oncology Journal
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    • 제7권2호
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    • pp.205-211
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    • 1989
  • 1984년 7월부터 1988년 9월까지 경북대학교병원 치료방사선과에서 소세포 폐암으로 진단되어 복합화학요법 및 방사선 병용치료를 받은 27명을 대상으로 치료성적을 분석하였다. 완전관해율은 $70\%$, 부분관해율은 $22\%$, 무반응은 $8\%$였다. 여자, 수행상태 HO, 방사선량 4500cGy이상, 화학요법 4회 이상, 그리고 혈청 enolase수치 30ng/m1 이하 등에서 완전관해율이 높게 나타났으나 통계적 의의는 없었다. 중앙생존기간은 10개월이었고 1년생존율과 2년 생존율은 각각 $40.7\%$$12.2\%$였다. 생존율을 높이는 인자로는 수험상태 HO (p<005), 완전관해 (p<0.05), 하학요법 4회 이상(p<005), 방사선량 4500 cGy이상 등으로 나타났으며, 성별과 예방적 전뇌조사는 영향을 미치지 않았다.

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