• 제목/요약/키워드: Toxicity Endpoints

검색결과 53건 처리시간 0.026초

알킬페놀류 화합물의 양서류 발생독성: 종설 (Developmental Toxicity of Alkylphenols in Amphibians: A Review)

  • 박찬진;안혜선;안효민;계명찬
    • 생태와환경
    • /
    • 제44권2호
    • /
    • pp.103-112
    • /
    • 2011
  • 내분비계장애물질과 같은 유기화합물에 의한 수계의 오염은 지구적인 양서류 감소의 원인으로 의심되고 있다. 양서류는 수정 후 변태에 이르는 생활사를 수중에서 진행하므로 수환경 오염물질에 의한 독성효과를 연구하기에 적합한 모델이다. 또한 양서류는 인간을 비롯한 육상척추동물과 발생학적으로 많은 공통점을 가지므로 공중보건학적 관점에서도 수환경 오염물질의 위해성 평가에 적항한 모델생물이다. 특정 화학물질이나 환경매체의 안전관리 기준을 설정하고 수환경의 독성물질 관리를 위해서는 다양한 독성종말점에서 독성정보가 필요하다. 알킬페놀류 화합물은 농업, 공업, 가정활동에 사용되고 있으며, 수환경 내에 잔류하여 다양한 수생동물에서 내분비계장애효과를 갖는다. 본 소고에서는 양서류의 배아, 유생을 대상으로 알킬페놀류 화합물의 종류별, 노출경로 및 농도, 노출 시기에 따른 발생장애와 발생기형 유발효과와 그 기작에 관한 국내외 자료를 정리하였다. 육수환경 잔류 오염물질의 중장기 노출독성 평가모델로서 양서류배아 발생독성평가법의 유용성을 제안하였다.

당뇨를 동반한 심부전 환자에 대한 beta-blocker의 유효성 평가 (Retrospective Evaluation for Efficacy and Tolerance of beta-blocker in Heart Failure Patients with Concomitant Diabetes)

  • 장선미;강민희;임성실;이준섭;이명구
    • 한국임상약학회지
    • /
    • 제16권2호
    • /
    • pp.113-122
    • /
    • 2006
  • Purpose: A retrospective study was performed to assess the efficacy and tolerance of ${\beta}-blocker$ administration in patients with heart failure and diabetes. Method: Records of 164 patients who were treated for the heart failure condition more than a year were studied retrospectively. Patients were divided into 4 groups based on their diabetes(DM) status and the administration of ${\beta}-blockers$ ($DM+{\beta}-blocker$ group: 14, DM w/o ${\beta}-blocker$: 19, No DM + ${\beta}-blocker$: 62, No DM + no ${\beta}-blocker$: 69). All patients had been receiving conventional therapy such as digoxin, ACE-I, ARB, diuretics, nitrates, aspirin, anticoagulants or lipid-lowering agents. The primary endpoints (death and hospital admission) were recorded during 1 year period and hemodynamic factors (HR, LVEF, SBP, DBP) were obtained from all patient groups before and after 12 months of ${\beta}-blocker$ treatment. To evaluate toxicity of ${\beta}-blocker$, SCr, BUN, AST, ALT and Alkaline phosphatase were obtained. Result: There were less death and hospital admission in DM + ${\beta}-blocker$ group than in DM without ${\beta}-blocker$ group (p=0.014). Relative risk of hospital admission for $DM+{\beta}-blocker$ group over no DM group was 1.17. Long term ${\beta}-blocker$ administration was associated with an improvement of heart rate in patients with DM (P< 0.02) with no significant improvement of LVEF, SBP, DBP. in DM patient. In patient without DM, ${\beta}-blocker$ was associated with improvement in LVEF, HR and DBP (P<0.01, P<0.03), but not in SBP. The incidence of toxicity was similar between the four group with no significant difference. Conculsion: Treatment of heart failure patients with ${\beta}-blocker$ appears to be beneficial in terms of hospital admission event and several hemodynamic factors. The toxicities of ${\beta}-blocker$ treatment were not significant and the treatment is generally well-tolerated in most of the heart failure patients.

  • PDF

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

  • Joo, Jin-Deok;Chang, Jong-Hee;Kim, Jeong-Hoon;Hong, Yong-Kil;Kim, Young-Hoon;Kim, Chae-Yong
    • Journal of Korean Neurosurgical Society
    • /
    • 제52권2호
    • /
    • pp.92-97
    • /
    • 2012
  • Objective : This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma. Methods : Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety. Results : A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted. Conclusion : This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.

내분비 교란성 DEHP의 항-에스트로젠 활성에 관한 연구 (Study on Anti-estrogenic Activity of DEHP as an Endocrine Disruption Chemical)

  • Kim, Eun-Joo
    • 한국환경보건학회지
    • /
    • 제29권2호
    • /
    • pp.7-15
    • /
    • 2003
  • DEHP는 대표적인 플라스틱 가소제 가운데 하나로서, 광범위하게 사용되고 있으며, 내분비계 장애물질로 분류퇴고 있다. 실제로 하천, 해양, 토양 등 광범위한 환경에서 검출되고 있지만, 이 물질이 수서 생물에 미치는 내분비교란 영향과 기작에 대해서는 거의 알려진 바가 없다. 본 연구에서는 송사리로 불리우는 Oryzias latipes(Japanese medaka)와, 유생 시기에 저니성 무척추 동물로 존재하다가 성충이 되는 Chironomus riparius를 대상으로 DEHP가 내분비 장애물질로서 생식작용에 미치는 영향에 대하여 연구하였다. 먼저, Japanese medaka를 부화 직후부터 3개월간 DEHP 1, 10, 50 $\mu\textrm{g}$/l의 농도로 노출시킨 결과 암놈의 혈중 비텔로제닌의 감소 ,생식소 지수인 GSI(Gonado Somatic Index) 감소. 난자 발달 저해 등이 관찰되었다. 또한, C. riparius를 산란 직후부터 DEHP에 노출시킨 경우에는 성체 출현률, 암수 비율, 산란률에서는 용량-반응 관계를 가진 변화가 발견되지 않았으나, 산란된 알의 부화율은 DEHP에 노출된 경우 유의하게 감소하는 것이 관찰되었다. 이러한 결과를 종합하여 볼 때. DEHP는 O. latpes와 C. riparius 모두 생식 작용에 영향을 미치며, 그 작용 기작은 일반적으로 발견되는 에스트로젠(estrogen) 활성이 아닌 암놈의 생식기관의 발달을 직, 간접적으로 저해함으로서 정상적인 알의 생성을 방해하는 이른바 항-에스트로젠 기작을 보이는 것으로 추정된다. 본 연구에서는 DEHP 위해성 평가를 위한 기본 자료로서, 생식작용 영향에 대한 새로운 자료를 제시하였다.

경막외 Morphine과 병합 투여되는 0.125%와 0.0625% Bupivacaine의 술 후 제통효과 및 부작용의 차이 (Differential Analgesic and Adverse Effects of 0.125% and 0.0625% Bupivacaine Coadministered Epiduraly with Morphine)

  • 이재민;최종호
    • The Korean Journal of Pain
    • /
    • 제12권1호
    • /
    • pp.48-53
    • /
    • 1999
  • Background: Despite the popularity of epidural bupivacaine-morphine infusions for postoperative pain management, the optimum concentrations and dosages of bupivacaine have not been determined. At present, due to the disadvantages conferred by intense motor block and the increased risk of toxicity, many trials focus on reducing bupivacaine concentration and thus the evaluation of concentrations less than 0.1% may be warranted. Methods: Forty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of two study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly 1 hr before the end of surgery and continuous epidural infusion was started using a two-day Infusor containing 4 mg of morphine in 100 ml of 0.125% bupivacaine (Group 0.125B, n=20) or 100 ml of 0.0625% bupivacaine (Group 0.0625B, n=20). Study endpoints included visual analog scales (VAS) for pain during rest and movement, sensory change and motor blockade. They were assessed at 2, 4, 8, 16, 24, 32, 40 and 48 hrs postoperatively. Results: For VAS during rest, no significance could be found between two groups over the course of study. But for VAS during movement, the 0.125B group showed more satisfactory results especially during early postoperative periods. For the incidence of complications, the 0.125B group revealed greater frequency of sensory change (25.0%) and motor blockade (10.0%) compared with the 0.0625B group. Conclusion: This study suggests that 0.0625% bupivacaine with morphine via epidural route was sufficient for pain control during rest but it was not satisfactory during movement especially in early postoperative periods. We also recommend that careful attention to motor blockade should be paid when using 0.125% bupivacaine.

  • PDF

Sweet BV 시술이 Rat의 중추신경계에 미치는 영향 - 기능관찰 종합평가를 이용하여- (Effects of Sweet Bee Venom on the Central Nervous System in Rats -using the Functional Observational Battery-)

  • 안중철;권기록
    • 대한약침학회지
    • /
    • 제14권3호
    • /
    • pp.19-45
    • /
    • 2011
  • Objectives: This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV-pure melittin, the major component of honey bee venom) on the central nervous system in rats. Methods: All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Male rats of 5 weeks old were chosen for this study and after confirming condition of rats was stable, Sweet BV was administered in thigh muscle of rats. And checked the effects of Sweet BV on the central nervous system using the functional observational battery (FOB), which is a neuro-toxicity screening assay composed of 30 descriptive, scalar, binary, and continuous endpoints. And home cage observations, home cage removal and handling, open field activity, sensorimotor reflex test/physiological measurements were conducted. Results: 1. In the home cage observation, there was not observed any abnormal signs in rats. 2. In the observation of open field activity, the reduction of number of unit areas crossed and rearing count was observed caused by Sweet BV treatment. 3. In the observation of handling reactivity, there was not observed any abnormal signs in rats. 4. In the observation of sensorimotor reflex tests/physiological measurements, there was not observed any neurotoxic signs in rats. 5. In the measurement of rectal temperature, treatment of Sweet BV did not showed great influences in the body temperature of rats. Conclusions: Above findings suggest that Sweet BV is relatively safe treatment in the central nervous system. But in the using of over dose, Sweet BV may the cause of local pain and disturbance of movement. Further studies on the subject should be conducted to yield more concrete evidences.

Essential Guidelines for Manufacturing and Application of Organoids

  • Sun-Ju Ahn;Sungin Lee;Dayeon Kwon;Sejeong Oh;Chihye Park;Sooyeon Jeon;Jin Hee Lee;Tae Sung Kim;Il Ung Oh
    • International Journal of Stem Cells
    • /
    • 제17권2호
    • /
    • pp.102-112
    • /
    • 2024
  • An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs and tissues and is used for evaluating the safety and effectiveness of drugs and the toxicity of industrial chemicals. Organoid technology is a new methodology that could replace testing on animals testing and accelerate development of precision and regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility of the production process and no internationally agreed standards for quality evaluation factors at endpoints. To overcome these barriers that hinder the regulatory acceptance and commercialization of organoids, Korea established the Organoid Standards Initiative in September 2023 with various stakeholders, including industry, academia, regulatory agencies, and standard development experts, through public and private partnerships. This developed general guidelines for organoid manufacturing and quality evaluation and for quality evaluation guidelines for organoid-specific manufacturing for the liver, intestines, and heart through extensive evidence analysis and consensus among experts. This report is based on the common standard guideline v1.0, which is a general organoid manufacturing and quality evaluation to promote the practical use of organoids. This guideline does not focus on specific organoids or specific contexts of use but provides guidance to organoid makers and users on materials, procedures, and essential quality assessment methods at end points that are essential for organoid production applicable at the current technology level.

Re-irradiation of unresectable recurrent head and neck cancer: using Helical Tomotherapy as image-guided intensity-modulated radiotherapy

  • Jeong, Songmi;Yoo, Eun Jung;Kim, Ji Yoon;Han, Chi Wha;Kim, Ki Jun;Kay, Chul Seung
    • Radiation Oncology Journal
    • /
    • 제31권4호
    • /
    • pp.206-215
    • /
    • 2013
  • Purpose: Re-irradiation (re-RT) is considered a treatment option for inoperable locoregionally recurrent head and neck cancer (HNC) after prior radiotherapy. We evaluated the efficacy and safety of re-RT using Helical Tomotherapy as image-guided intensity-modulated radiotherapy in recurrent HNC. Materials and Methods: Patients diagnosed with recurrent HNC and received re-RT were retrospectively reviewed. Primary endpoint was overall survival (OS) and secondary endpoints were locoregional control and toxicities. Results: The median follow-up period of total 9 patients was 18.7 months (range, 4.1 to 76 months) and that of 3 alive patients was 49 months (range, 47 to 76 months). Median dose of first radiotherapy and re-RT was 64.8 and 47.5 $Gy_{10}$. Median cumulative dose of the two courses of radiotherapy was 116.3 $Gy_{10}$ (range, 91.8 to 128.9 $Gy_{10}$) while the median interval between the two courses of radiation was 25 months (range, 4 to 137 months). The response rate after re-RT of the evaluated 8 patients was 75% (complete response, 4; partial response, 2). Median locoregional relapse-free survival after re-RT was 11.9 months (range, 3.4 to 75.1 months) and 5 patients eventually presented with treatment failure (in-field failure, 2; in- and out-field failure, 2; out-field failure, 1). Median OS of the 8 patients was 20.3 months (range, 4.1 to 75.1 months). One- and two-year OS rates were 62.5% and 50%, respectively. Grade 3 leucopenia developed in one patient as acute toxicity, and grade 2 osteonecrosis and trismus as chronic toxicity in another patient. Conclusion: Re-RT using Helical Tomotherapy for previously irradiated patients with unresectable locoregionally recurrent HNC may be a feasible treatment option with long-term survival and acceptable toxicities.

"Sandwich" Chemotherapy (CT) with Radiotherapy (RT) Improves Outcomes in Patients with Stage IE/IIE Extranodal Natural Killer (NK)/T-cell Lymphomas

  • Zhang, Jing;Zhu, Meng-Yuan;Wang, Liang;Wang, Hua;Wang, Wei-Da;Geng, Qi-Rong;Lu, Yue
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제14권7호
    • /
    • pp.4061-4066
    • /
    • 2013
  • The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.

Euglena 운동성 측정장치를 이용한 생태독성평가 (Ecotoxicity Test Using E. agilis Biomonitoring System)

  • 이정아;김경남;박다경
    • 환경생물
    • /
    • 제34권2호
    • /
    • pp.124-131
    • /
    • 2016
  • Euglena agilis의 운동성 반응을 자동으로 측정하는 장치인 E. agilis 시스템 (E-Tox)을 이용하여 8종의 중금속 (Ag, Cd, Cr(VI), Cu, Hg, Ni, Pb, Zn)에 대한 독성시험을 실시하였다. E. agilis 운동성 시험 (biomonitoring test)으로부터 도출된 $EC_{50}$과 문헌상의 자료 조사로 얻은 기존 생태독성 시험 생물 종들(D. magna, V. fischeri, 그리고 E. gracilis)의 $EC_{50}$을 비교하여 시험물질에 대한 E. agilis의 독성 민감도를 평가하였다. 또한 축산폐수 방류수, 도금폐수 방류수, 도금폐수 1차 처리 시료에 대해 D. magna 급성 독성시험과 E. agilis 운동성 반응 시험을 수행 후 TU를 비교하여 E. agilis 운동성 시험의 현장 적용 가능성을 평가하였다. E. agilis는 시험 중금속에 대해 D. magna보다 독성민감도가 전반적으로 낮았으나 V. fischeri 또는 E. gracilis와 유사하거나 좀 더 민감하였다. E. agilis는 D. magna test로 유독성으로 판명된 도금폐수 1차 처리수에 대해 신속한 독성반응을 나타내었다. E-Tox 시스템은 기존의 생태독성시험장비에 비해 빠르고 작동이 간편한 자동화 기기라는 장점이 있다. 본 연구의 결과 E-Tox 시스템을 이용한 E. agilis 운동성 시험은 향후 독성폐수에 대한 조기경보를 위한 생태독성시험법으로 적용될 수 있을 것으로 판단된다.