• Title/Summary/Keyword: Toxicity Sensitivity

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THERMO-SENSITIVITY OF N-VINYL PYRROLODONE-CO-2- HYDROXYETHYLMETHACRYLATE HYDROGELS

  • Irina Nam;Park, Jung-Ki;Lee, Seong-Nam;Sung, Shi-Joon;Min, Yong-Jin
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2004.05a
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    • pp.9-15
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    • 2004
  • The copolymerization of HEMA with different hydrophilic and hydrophobic co-monomers allows for the manipulation of their intrinsic properties. 2-Hydroxyethylmethacrylate (HEMA)-based hydrogels thus are of great interest due to their outstanding physico-mechanical properties and chemical stability. The idea to use HEMA in order to create thermo-sensitive polymers was based on our assumption that thermal-sensitivity comes from a suitable hydrophilic-hydrophobic balance of macromolecules. In this work we have chosen N-vinyl pyrrolidone as a hydrophilic co-monomer with the relatively hydrophobic HEMA due to its good polymerizing properties as well as its non-toxicity in a polymer state and deserved recognition as a biocompatible material. As a result, copolymerization of NVP and HEMA was successful in obtaining new types of thermo-sensitive polymers composed of hydrophilic and hydrophobic monomers.

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Establishment of Marine Ecotoxicological Standard Method for Larval Fish Survival Test (어류 자어의 사망률을 이용한 해양생태독성시험 방법에 관한 연구)

  • Park, Gyung-Soo;Kang, Ju-Chan;Yoon, Sung-Jin;Lee, Seung-Min;Hwang, Un-Ki
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.13 no.2
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    • pp.140-146
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    • 2008
  • Marine ecotoxicological standard method using fish larvae was established with the standard test species of Oryzias latipes(Japanese Medaka) and Paralichthys olivaceus(flounder) and with the 7 day $LC_{50}$ as endpoint. Test method referred to the USEPA(1994) with the replacement of test species found in the Korean water. Standard test species were selected in terms of the species supply and ecological importance in Korean waters. Japanese medaka can be reared with small tanks in the lab and has wide tolerance on salinity, and flounder eggs can be easily obtained from commercial fish hatcheries. General conditions for larval fish toxicity test are as follows. The possible salinity ranges for toxicity test were $0{\sim}35\;psu$ for medaka and >20 psu for flounder. Test type was designated as static non-renewal test if the dissolved oxygen in the test chamber does not fall below 4.0 mg/L. Ages of test species were selected as 7 days after hatched for medaka(about 5 mm TL) and 25 days for flounder(about 10 mm TL) because of the low natural mortality after these periods. Test can be accepted when the survival rates are over 80% in control. Also, species sensitivity on standard reference materials(copper, cadmium or zinc) must be provided with the toxicity test results.

Severe Acidosis after Massive Metformin Overdose (혈당 강하제 metformin 중독 후 발생한 심각한 산혈증 1례)

  • Kim, Bo-In;Jung, Jin-Hee;Eo, Eun-Kyung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.6 no.1
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    • pp.42-44
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    • 2008
  • Metformin which is an oral hypoglycemic agents, acts by enhancing insulin sensitivity, decreasing hepatic glucose production and increasing peripheral utilization of glucose. Deliberate self poisoning with oral hypoglycemic agents is rare. The lactic acidosis associated with metformin toxicity is well described in the medical literature. Metformin overdose even in otherwise healthy patients may produce a profound and life threatening lactic acidosis. We report a case of massive metformin ingestion(75g) in a patient presenting with lactic acidosis and hypotension. She died 24h after presenting to our emergency department despite bicarbonate treatment and hemofiltration therapy.

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Ultra-sensitive Determination of Salinomycin in Serum Using ICP-MS with Nanoparticles

  • Cho, H.K.;Lim, H.B.
    • Bulletin of the Korean Chemical Society
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    • v.35 no.11
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    • pp.3195-3198
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    • 2014
  • An ultra-sensitive detection method for small molecules such as antibiotics was developed using ICP-MS with magnetic and $TiO_2$ nanoparticles. Since most of the antibiotics are too small to employ a sandwich-type extraction through an immunoreaction, a non-specific platform was employed, in which the target was extracted by magnetic separation, followed by tagging with $TiO_2$ nanoparticles of 11.2 nm for ICP-MS measurement. The detection limit for salinomycin obtained from spiked serum samples was $0.4ag\;mL^{-1}$ (${\pm}10.3%$), which was about $1.5{\times}10^6$ times lower than that of LC-MS/MS and about $1.2{\times}10^{11}$ times better than that of ELISA. Such an excellent sensitivity enabled us to study the toxicity of antibiotics exposed to human beings by determining them in serum.

Evaluation of the sub-lethal toxicity of Cu, Pb, bisphenol A and polychlorinated biphenyl to the marine dinoflagellate Cochlodinium polykrikoides

  • Ebenezer, Vinitha;Ki, Jang-Seu
    • ALGAE
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    • v.27 no.1
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    • pp.63-70
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    • 2012
  • Algae are sensitive to a wide range of pollutants, and are effective bioindicators in ecotoxicity assessments. Here, we evaluated the sub-lethal sensitivity of the marine dinoflagellate Cochlodinium polykrikoides upon exposure to copper (Cu), lead (Pb), bisphenol A (BPA), and Aroclor 1016 (polychlorinated biphenyl, PCB). Toxic effects were assessed by observations of the reduction in cell counts and chlorophyll a levels after exposure to each toxicant. C. polykrikoides displayed dose-dependent, sigmoidal responses when exposed to the tested chemicals. $EC_{50}$-72 h values for Cu, Pb, BPA, and PCB were 12.74, 46.70, 68.15, and $1.07mg\;L^{-1}$, respectively. PCB, which is an endocrine-disrupting chemical, was the most sensitive, proving its toxic effect on the dinoflagellate. This study provides baseline data on the toxic effects of commonly used heavy metals and endocrine-disrupting chemicals to a marine dinoflagellate.

A Review of Dose Finding Methods and Theory

  • Cheung, Ying Kuen
    • Communications for Statistical Applications and Methods
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    • v.22 no.5
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    • pp.401-413
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    • 2015
  • In this article, we review the statistical methods and theory for dose finding in early phase clinical trials, where the primary objective is to identify an acceptable dose for further clinical investigation. The dose finding literature is initially motivated by applications in phase I clinical trials, in which dose finding is often formulated as a percentile estimation problem. We will present some important phase I methods and give an update on new theoretical developments since a recent review by Cheung (2010), with an aim to cover a broader class of dose finding problems and to illustrate how the general dose finding theory may be applied to evaluate and improve a method. Specifically, we will illustrate theoretical techniques with some numerical results in the context of a phase I/II study that uses trinary toxicity/efficacy outcomes as basis of dose finding.

Mitochondrial DNA Somatic Mutation in Cancer

  • Kim, Aekyong
    • Toxicological Research
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    • v.30 no.4
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    • pp.235-242
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    • 2014
  • Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.

Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer

  • Luealon, Phanida;Khempech, Nipon;Vasuratna, Apichai;Hanvoravongchai, Piya;Havanond, Piyalamporn
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.799-805
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    • 2016
  • Background: There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. Objective: To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. Materials and Methods: A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Results: Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All four alternative treatments increased life expectancy. Life expectancy of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 0.510, 0.513, 0.566, and 0.570 years, respectively. The total cost of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 113,000, 124,302, 139,788 and 151,135 Baht, respectively. PLD followed by topotecan had the highest expected quality-adjusted life-years but was the most expensive of all the above strategies. The incremental cost-effectiveness ratios (ICER) of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 344,643, 385,322, 385,856, and 420,299 Baht, respectively. Conclusions: All of the second-line chemotherapy strategies showed certain benefits due to an increased life-year gained compared with best supportive care. Moreover, gemcitabine as second-line chemotherapy followed by best supportive care in progressive disease case was likely to be more effective strategy with less cost from health care provider perspective. Gemcitabine was the most cost-effective treatment among all four alternative treatments. ICER is only an economic factor. Treatment decisions should be based on the patient benefit.

Effect of Cu Species Distribution in Soil Pore Water on Prediction of Acute Cu Toxicity to Hordeum vulgare using Terrestrial Biotic Ligand Model (토양 공극수 내 Cu의 존재형태가 terrestrial biotic ligand model을 이용한 보리의 급성독성 예측에 미치는 영향)

  • An, Jinsung;Jeong, Buyun;Lee, Byungjun;Nam, Kyoungphile
    • Journal of Soil and Groundwater Environment
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    • v.22 no.5
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    • pp.30-39
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    • 2017
  • In this study, the predictive toxicity of barley Hordeum vulgare was estimated using a modified terrestrial biotic ligand model (TBLM) to account for the toxic effects of $CuOH^+$ and $CuCO_3(aq)$ generated at pH 7 or higher, and this was compared to that from the original TBLM. At pH values higher than 7, the difference in $EA_{50}\{Cu^{2+}\}$ (half maximal effective activity of $Cu^{2+}$) between the two models increased with increasing pH. As Mg concentration increased from 8.24 to 148 mg/L in the pH range of 5.5 to 8.5, the difference in $EA_{50}\{Cu^{2+}\}$ increased, and it reached its maximum at pH 8. The difference in $EC_{50}[Cu]_T$ (half maximal effective concentration of Cu) between the two models increased as dissolved organic carbon (DOC) concentration increased when pH was above 7. Thus, for soils with alkaline pH, the toxic effect of $CuOH^+$ and $CuCO_3(aq)$ are greater at higher salt and DOC concentrations. The acceptable Cu concentration in soil porewater can be estimated by the modified TBLM through deterministic method at pH levels higher than 7, while combination of TBLM and species sensitivity distribution through the probabilistic method could be utilized at pH levels lower than 7.

Effect of GeO2 on embryo development and photosynthesis in Fucus vesiculosus (Phaeophyceae)

  • Tarakhovskaya, Elena R.;Kang, Eun-Ju;Kim, Kwang-Young;Garbary, David J.
    • ALGAE
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    • v.27 no.2
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    • pp.125-134
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    • 2012
  • Germanium dioxide ($GeO_2$) has been used for many years in the cultivation of red and green algae as a means of controlling the growth of diatoms. Brown algae are sensitive to $GeO_2$, however, the basis of this sensitivity has not been characterized. Here we use embryos of $Fucus$ $vesiculosus$ to investigate morphological and physiological impacts of $GeO_2$ toxicity. Morphometric features of embryos were measured microscopically, and physiological features were determined using pulse amplitude modulated (PAM) fluorometry. At 5 mg $L^{-1}$ $GeO_2$, embryos grew slower than controls and developed growth abnormalities. After 24 h, initial zygote divisions were often oblique rather than transverse. Rhizoids had inflated tips in $GeO_2$ and were less branched, and apical hairs were deformed, with irregularly aligned, spheroidal cells. Minimum fluorescence ($F_0$) showed minor differences over the 10 days experiment, and pigment levels (chlorophylls $a$, $c$ and total carotenoids) showed no difference after 10 days. Optimum quantum yield increased from ca. 0.52 at 24 h to 0.67 at 5 days, and $GeO_2$-treated embryos had higher mean values (significant at 3 and 5 days). Optimum quantum yield of photosystem II (${\Phi}_{PSII}$) was stable in control thalli after 5 days, but declined significantly in $GeO_2$. Addition of silica (as $SiO_2$) did not reverse the effects of $GeO_2$. These results suggest that $GeO_2$ toxicity in brown algae is associated with negative impacts at the cytological level rather than metabolic impacts associated with photosynthesis.