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The concept of the exposure standard
Published in Sue Reed, Dino Pisaniello, Geza Benke, Kerrie Burton, Principles of Occupational Health & Hygiene, 2020
When the body is exposed to two or more contaminants, an additive effect results when the contaminants have the same target organ or the same mechanism of action. For example, ethyl acetate and methyl ethyl ketone both affect the central nervous system. In this situation, the total effect upon the body equals the sum of effects from the individual substances. For substances whose effects are purely additive, conformity with the standard results when C1L1+C2L2+…+CnLn≤1
The concept of the exposure limit for workplace health hazards
Published in Sue Reed, Dino Pisaniello, Geza Benke, Principles of Occupational Health & Hygiene, 2020
When the body is exposed to two or more contaminants, an additive effect results when the contaminants have the same target organ or the same mechanism of action. For example, ethyl acetate and methyl ethyl ketone both affect the central nervous system. In this situation, the total effect upon the body equals the sum of effects from the individual substances. For substances whose effects are purely additive, conformity with the standard results when C1L1+C2L2+…+CnLn≤1 where C1, C2 … Cn are the average measured airborne concentrations of the particular substances 1, 2 … n, and L1, L2 … Ln are the appropriate exposure standards for the individual substances.
Escherichia coli
Published in Yoshikatsu Murooka, Tadayuki Imanaka, Recombinant Microbes for Industrial and Agricultural Applications, 2020
Hisashi Yasueda, Hiroshi Matsui
It has been reported that production of abnormal proteins, such as incomplete proteins, with puromycin or streptomycin, or cloned proteins (e.g., human tissue plasminogen activator), causes an increase in Ion transcription [68]. This induction process requires the heat-shock regulatory gene (htpR) and is not seen in htpR mutant cells. The htpR gene encodes a sigma factor (<x32), which is apparently essential for various cellular functions. Nonsense (amber) mutations of htpR, suppressed by a temperature-sensitive suppressor, were constructed and these mutants had a lower capacity to degrade abnormal or incomplete proteins than wild-type cells. It was also demonstrated that the reduction in proteolysis equals or exceeds that in Ion mutants, and is particularly great in htpR Ion double mutants [69,70]. Buell et al. reported that cells with a double mutation, Ion htpR, effectively accumulated the labile polypeptide somatomedin C by increasing its half-life, and found that the two mutations had an additive effect [71]. Also, Mandecki et al. were able to increase the expression of a human complement factor (C5a) by using a strain with the htpR mutation [72]. Thus, it seems that strains with htpR Ion mutations may be very useful for increasing the stability of many foreign proteins in E. coli. It is known that T4 infection of E. colidoes not affect the degradation of normal proteins, but the turnover of abnormal proteins is substantially inhibited [73]. One of the genes responsible for this effect is the T4 pin (proteolysis mhibition) gene. Simon et al. cloned the pin gene and found that it increased the stability of cloned mature human fibroblast interferon in E. coli [74]. However, it was also shown that pin acts to block Lon proteinase activity [75].
Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Dong-Jin Ye, Yeo-Jung Kwon, Hyoung-Seok Baek, Eunah Cho, Tae-Uk Kwon, Young-Jin Chun
Combination index values indicate the antagonistic (Combination index > 1), additive (Combination index = 1), or synergistic (Combination index < 1) role for different chemical-chemical concentrations and effect levels. The synergistic effect between nutlin-3a and auranofin was assessed by the isobologram method (Tallarida 2001). Briefly, IC50 values of nutlin-3a and auranofin were plotted on the x- and y-axes, respectively, to form a straight line. The isobologram datum point represents the actual IC50 value of nutlin-3a combined with auranofin. If the datum point is located on or near the line, this indicates an additive effect, a datum point located below the line indicates synergism between two chemicals, and a datum point above the line indicates antagonism.
Synthesis and characterization of novel P(HEMA-LA-MADQUAT) micelles for co-delivery of methotrexate and Chrysin in combination cancer chemotherapy
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Soodabeh Davaran, Hamed Fazeli, Aliyeh Ghamkhari, Fariborz Rahimi, Ommoleila Molavi, Maryam Anzabi, Roya Salehi
The in vitro cytotoxicity was investigated on MCF-7 cells using MTT assay method. The cytotoxic effects were evaluated by MTX and Chrysin as the references in comparison to MTX@Chrysin-loaded P(HEMA-LA-MADQUAT). The MCF-7 cells were trypsinized, harvested and seeded in 96 well plates (1 × 104 cells per well). After overnight incubation, the cells were treated with different doses of pure solutions of MTX and chrysin separately, MTX + chrysin solution, blank micelles, MTX in micelles, chrysin in micelles and MTX@Chrysin-loaded P(HEMA-LA-MADQUAT) micelle with combined concentrations of 10, 25, 50, 75,100 μg.mL−1 for the two drugs. MCF-7 cells were also treated with 1000 μg.mL−1 in order to evaluate the probable cytotoxicity of P(HEMA-LA-MADQUAT) micelle. Untreated cells were used as negative control. After 48 h, the media was removed and 200 μL media containing 50 μL of MTT solution was added to each well and incubated for another 4 h. Eventually, the remaining MTT solution was removed, the produced Formosan crystals were dissolved in DMSO and absorbance was read at 570 nm by a spectrophotometric plate reader, ELx 800 (Biotech, San Francisco, CA, U.S.A.). In addition, combination index (CI) values were calculated using CompuSyn v.1 software. CI value of 1 shows an additive effect; while a CI < 1 exhibits synergism and CI > 1 reveals an antagonism
Combined treatment with auranofin and trametinib induces synergistic apoptosis in breast cancer cells
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Min-Kyung Joo, Sangyun Shin, Dong-Jin Ye, Hong-Gyu An, Tae-Uk Kwon, Hyoung-Seok Baek, Yeo-Jung Kwon, Young-Jin Chun
Briefly, IC50 values of trametinib and auranofin were plotted on the x- and y-axes, respectively, to obtain a straight line. The isobologram datum point represents the actual IC50 value of trametinib combined with auranofin. If the datum point is located on or near the line, this indicates an additive effect; a datum point located below the line indicates synergism between two chemicals, whereas a datum point above the line indicates antagonism.