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1
Neumann, Heike, and Dietrich Werner. "Gene Expression of Medicago sativa Inoculated with Sinorhizobium meliloti as Modulated by the Xenobiotics Cadmium and Fluoranthene." Zeitschrift für Naturforschung C 55, no. 3-4 (2000): 222–32. http://dx.doi.org/10.1515/znc-2000-3-414.
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Abstract Alfalfa plants (Medicago sativa cv. Europe) inoculated with Sinorhizobium meliloti 2011 (formerly Rhizobium meliloti, de Lajudie et al., 1994) were cultivated for 14 days under standardized growth conditions in mineral medium with addition of the heavy metal cadmium or the polycyclic aromatic hydrocarbon fluoranthene. These xenobiotics significantly reduced the numbers of root nodules before any visible damage to the plant could be detected. EC10. EC50, and EC90 (effective concentrations reducing nodulation, shoot and root fresh weight by 10, 50, or 90% compared to the control without pollutant) were calculated. EC50 for cadmium ranged from 5.8 jam (nodulation) to more than 20 μᴍ (root fresh weight). Testing fluoranthene resulted in an EC50 of 2.5 μg cm-2 for nodulation, and EC50 values of more than 35 μg cm-2 for shoot and root biomass production, indicating that the effect parameter nodulation is 10-fold more sensitive than shoot and root fresh weight. With m RNA differential display techniques the effects of both xenobiotics on gene expression in alfalfa root systems were studied. 37 differentially displayed transcripts were detected. Two of them, called DDMs1 and DDMs2, were confirmed by northern hybridization to be down-regulated in the presence of the xenobiotics. The expression of transcript DDMs1 was enhanced in alfalfa control plants inoculated with rhizobia, the transcript level was increased 2.5-3-fold compared to non-inoculated plants. This positive effect of nodulation was suppressed, partly by 35 μg cm-2 fluoranthene and totally by 20 μᴍ cadmium. The decrease in DDMsl transcription was highly affected by the cadmium concentration with an EC50 of 5.9 μᴍ . Compared to nodulation, almost identical EC10, EC50. and EC90 values were found for DDMsl expression. Sequence analysis of DDMsl revealed a significant overall homology (50% identity) to a hypothetical protein from Arabidopsis thaliana with high similarity to a copper transporting ATPase. High levels of transcript DDMs2 were observed in control plants with a 50% decrease in the xenobiotic-treated plants. DDM s2 gave a strong homology (82% identity) to the cytoplasmatic 60S ribosomal protein L18 from Arabidopsis thaliana.
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Wang, Mei, Weirong Zhang, Jiaojiao Lu, Yanbo Huo, and Jing Wang. "The Effects of Antofine on the Morphological and Physiological Characteristics of Phytophthora capsici." Molecules 29, no. 9 (2024): 1965. http://dx.doi.org/10.3390/molecules29091965.
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Phytophthora capsici is an important plant pathogenic oomycete that causes great losses to vegetable production around the world. Antofine is an important alkaloid isolated from Cynanchum komarovii Al. Iljinski and exhibits significant antifungal activity. In this study, the effect of antofine on the mycelial growth, morphology, and physiological characteristics of P. capsici was investigated using colorimetry. Meanwhile, the activity of mitochondrial respiratory chain complexes of P. capsici was evaluated following treatment with a 30% effective concentration (EC30), as well as EC50 and EC70, of antofine for 0, 12, 24, and 48 h. The results showed that antofine had a significant inhibitory effect against P. capsici, with an EC50 of 5.0795 μg/mL. After treatment with antofine at EC50 and EC70, the mycelia were rough, less full, and had obvious depression; they had an irregular protrusion structure; and they had serious wrinkles. In P. capsici, oxalic acid and exopolysaccharide contents decreased significantly, while cell membrane permeability and glycerol content increased when treated with antofine. Reactive oxygen species (ROS) entered a burst state in P. capsici after incubation with antofine for 3 h, and fluorescence intensity was 2.43 times higher than that of the control. The activities of the mitochondrial respiratory chain complex II, III, I + III, II + III, V, and citrate synthase in P. capsici were significantly inhibited following treatment with antofine (EC50 and EC70) for 48 h compared to the control. This study revealed that antofine is likely to affect the pathways related to the energy metabolism of P. capsici and thus affect the activity of respiratory chain complexes. These results increase our understanding of the action mechanism of antofine against P. capsici.
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Matheron, M. E., and M. Porchas. "Impact of Azoxystrobin, Dimethomorph, Fluazinam, Fosetyl-Al, and Metalaxyl on Growth, Sporulation, and Zoospore Cyst Germination of Three Phytophthora spp." Plant Disease 84, no. 4 (2000): 454–58. http://dx.doi.org/10.1094/pdis.2000.84.4.454.
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In vitro activity of azoxystrobin, dimethomorph, and fluazinam on growth, sporulation, and zoospore cyst germination of Phytophthora capsici, P. citrophthora, and P. parasitica was compared to that of fosetyl-Al and metalaxyl. The 50% effective concentration (EC50) values for)inhibition of mycelial growth of the three pathogens usually were lowest for dimethomorph and (metalaxyl, ranging from <0.1 to 0.38 μg/ml. However, the 90% effective concentration (EC90) levels for dimethomorph always were lower than the other four tested compounds, with values ranging from 0.32 to 1.6 μg/ml. Mycelial growth of P. capsici, P. citrophthora, and P. parasitica was least affected by azoxystrobin and fluazinam, with estimated (EC90) values >3,000 μg/ml. Reduction of sporangium formation by P. capsici, P. citrophthora, and P. parasitica in the presence of dimethomorph at 1 μg/ml was significantly greater than that recorded for the same concentration of azoxystrobin, fluazinam, and fosetyl-Al. For the three species of Phytophthora, zoospore motility was most sensitive to fluazinam (EC50 and EC90 values of <0.001 μg/ml) and (least sensitive to fosetyl-Al, with (EC50 and EC90 values ranging from 299 to 334 and 518 to 680 μg/ml, respectively). Germination of encysted zoospores of P. capsici, P. citrophthora, and P. parasitica was most sensitive to dimethomorph (EC50 and EC90 values ranging from 3.3 to 7.2 and 5.6 to 21 μg/ml, respectively), intermediate in sensitivity to fluazinam (EC50 and EC90 from 18 to 108 and 67 to >1,000 μg/ml, respectively) and metalaxyl (EC50 and EC90 from 32 to 280 and 49 to 529 μg/ml, respectively), and lowest in sensitivity to azoxystrobin and fosetyl-Al (EC50 and EC90 from 256 to >1,000 μg/ml). The activity of azoxystrobin, dimethomorph, and fluazinam on one or more stages of the life cycle of P. capsici, P. citrophthora, and P. parasitica suggests that these compounds potentially could provide Phytophthora spp. disease control comparable to that of the established fungicides fosetyl-Al and metalaxyl.
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Padilla Suarez, Edith Guadalupe, Jesús G. Zorrilla, Marisa Spampinato, et al. "Toxicity Assessment of (4Z)-Lachnophyllum and (4Z,8Z)-Matricaria Lactones: Implications for Environmental Safety of Bioherbicides." Toxins 17, no. 4 (2025): 169. https://doi.org/10.3390/toxins17040169.
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(4Z,8Z)-Matricaria lactone (MAT) and (4Z)-lachnophyllum lactone (LAC) are natural acetylenic furanones with bioherbicidal potential. This study evaluates their possibilities and ecotoxicological impact on aquatic (Aliivibrio fischeri, Raphidocelis subcapitata, and Daphnia magna) and terrestrial (Caenorhabditis elegans, Lepidum sativum) model organisms. MAT exhibited rapid degradation, with 90% decomposition within 24 h and over 98% by day 16, while LAC was more stable, degrading by only 8.5% in 24 h and 67% by day 16. Despite its rapid breakdown, MAT exhibited higher acute toxicity to A. fischeri (EC10 = 0.063 mg L−1; EC50 = 0.642 mg L−1) compared to LAC (EC10 = 0.524 mg L−1; EC50 = 8.078 mg L−1). Toxicity patterns in R. subcapitata differed, with MAT promoting slightly higher growth compared to the control, suggesting hormetic effects (EC10 = 3.417 mg L−1; EC50 = 4.520 mg L−1), while LAC inhibited growth concentration (EC10 = 0.304 mg L−1; EC50 = 9.880 mg L−1). Both compounds immobilized D. magna, with LAC showing greater delayed toxicity (EC50 = 1.728 mg L−1 vs. MAT EC50 = 2.239 mg L−1). Furthermore, for L. sativum, there were no effects on the germination, but effects were observed in the lengths of the shoots (LAC EC50 = 85.89 mg L−1 vs. MAT EC50 = 82.30 mg L−1). In contrast, C. elegans showed no mortality, suggesting lower terrestrial toxicity. These findings suggest that MAT and LAC may pose risks to aquatic ecosystems through runoff or leaching, necessitating further studies on their degradation products, soil microbiota, and non-target terrestrial organisms. Comparative analyses with conventional herbicides highlight MAT and LAC as selective, lower-impact alternatives. Future research should focus on their effects on terrestrial organisms, the ecological safety of degradation products, and large-scale bioassays to ensure their sustainability in agriculture.
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Noel, Zachary A., Jie Wang, and Martin I. Chilvers. "Significant Influence of EC50 Estimation by Model Choice and EC50 Type." Plant Disease 102, no. 4 (2018): 708–14. http://dx.doi.org/10.1094/pdis-06-17-0873-sr.
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The effective control to 50% growth inhibition (EC50) is a standard statistic for evaluating dose-response relationships. Many statistical software packages are available to estimate dose-response relationships but, recently, an open source package (“drc”) in R has been utilized. This package is highly adaptable, having many models to describe dose-response relationships and flexibility to describe both hormetic relationships and absolute and relative EC50. These models and definitions are generally left out of phytopathology literature. Here, we demonstrate that model choice and type of EC50 (relative versus absolute) can matter for EC50 estimation using data from Pythium oopapillum and Fusarium virguliforme. For some P. oopapillum isolates, the difference between absolute and relative EC50 was significant. Hormetic effects changed F. virguliforme EC50 distributions, leading to higher estimates than when using four- or three-parameter log-logistic models. Future studies should pay careful attention to model selection and interpretation in EC50 estimation and clearly indicate which model and EC50 measure (relative versus absolute) was used. We provide guidelines for model choice and interpretation for those wishing to set up experiments for accurate EC50 estimation.
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Stadtlander, Klaus, and Heidemarie Lawohnus. "Yeast Cells as a Test System for Evaluating the Toxicity of Chemicals." Alternatives to Laboratory Animals 17, no. 3 (1990): 203–6. http://dx.doi.org/10.1177/026119299001700314.
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The first 13 substances of the MEIC (multicentre evaluation study of in vitro cytotoxicity) project were tested in a test system in which the generation time of yeast cells in their logarithmic growth phase was used as the endpoint. Toxic effects, expressed as EC10, EC20 or EC50 values, were correlated with octanol/water partition coefficients. The correlation was found to be very high, indicating that the lipophilicity of substances is a key parameter for describing the toxicity of chemicals.
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Dias, Joao D., Torben Pottgiesser, Jan Hartmann, Daniel Duerschmied, Christoph Bode, and Hardean E. Achneck. "Comparison of three common whole blood platelet function tests for in vitro P2Y12 induced platelet inhibition." Journal of Thrombosis and Thrombolysis 50, no. 1 (2019): 135–43. http://dx.doi.org/10.1007/s11239-019-01971-1.
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Abstract In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0–7500 ng/mL) and/or ASA (0–3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19–9153 ng/mL), followed by TEG®6s (144–2589 ng/mL), and VerifyNow® (191–1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.
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Gupta, S., M. M. Thapar, W. H. Wernsdorfer, and A. Björkman. "In Vitro Interactions of Artemisinin with Atovaquone, Quinine, and Mefloquine against Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 46, no. 5 (2002): 1510–15. http://dx.doi.org/10.1128/aac.46.5.1510-1515.2002.
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ABSTRACT The interactions of artemisinin with atovaquone, quinine, and mefloquine were investigated in three Plasmodium falciparum strains (strains F-32, FCR-3, and K-1) by an in vitro culture assay. The parasites were cultured for 48 h in the presence of different concentrations and proportions of two drugs at a time in a checkerboard design. The response parameters were determined, and the sums of the fractional inhibitory concentrations (ΣFICs) of the drug combinations were calculated for different degrees of inhibition (50% effective concentration [EC50], EC90, and EC99). Within therapeutically relevant molar ratios (19 to 200), the combination of quinine and artemisinin showed mean ΣFICs of 1.71 at the EC50, 0.36 at the EC90, and 0.13 at the EC99, indicating increasing synergism. Within the range of molar ratios of 4.3 to 50, the combination of mefloquine and artemisinin yielded mean ΣFCIs of 0.93, 0.44, and 0.31 at the EC50, EC90, and EC99, respectively, indicating synergism. The atovaquone combination showed additive activity to synergism at atovaquone/artemisinin proportions considered relevant to the in vivo situation, i.e., between 4.3 and 200, with the mean ΣFICs decreasing from 1.34 at the EC50 to 0.85 and 0.23 at the EC90 and EC99, respectively. Interstrain differences in the degree of drug interaction were seen with the three strains for all combinations. Synergism was most consistent with quinine.
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Picone, Marco, Gabriele Distefano, Davide Marchetto, et al. "Inhibition of Larval Development of Marine Copepods Acartia tonsa by Neonicotinoids." Toxics 10, no. 4 (2022): 158. http://dx.doi.org/10.3390/toxics10040158.
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Neonicotinoids (NEOs) are neurotoxic pesticides widely used in agriculture due to their high effectiveness against pest insects. Despite their widespread use, very little is known about their toxicity towards marine organisms, including sensitive and ecologically relevant taxa such as copepods. Thus, we investigated the toxicity of five widely used NEOs, including acetamiprid (ACE), clothianidin (CLO), imidacloprid (IMI), thiacloprid (THI), and thiamethoxam (TMX), to assess their ability to inhibit the larval development of the copepod Acartia tonsa. The more toxic NEOs were ACE (EC50 = 0.73 μg L−1), TMX (EC50 = 1.71 μg L−1) and CLO (EC50 = 1.90 μg L−1), while the less toxic compound was IMI (EC50 = 8.84 μg L−1). Early life-stage mortality was unaffected by NEOs at all of the tested concentrations. The calculated toxicity data indicated that significant effects due to ACE (EC20 = 0.12 μg L−1), THI (EC20 = 0.88 μg L−1) and TMX (EC20 = 0.18 μg L−1) are observed at concentrations lower than established chronic aquatic life benchmarks reported by USEPA for freshwater invertebrates. Nevertheless, since environmental concentrations of NEOs are generally lower than the threshold concentrations we calculated for A. tonsa, the effects may be currently of concern only in estuaries receiving wastewater discharges or experiencing intense runoff from agriculture.
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Eugene, Andy R. "Fluoxetine pharmacokinetics and tissue distribution quantitatively supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per day." F1000Research 10 (October 13, 2022): 477. http://dx.doi.org/10.12688/f1000research.53275.3.
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Background. Various in vitro studies have shown fluoxetine inhibits multiple variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen causing the coronavirus disease 2019 (COVID-19) worldwide pandemic and multiple observational clinical studies have shown that patients receiving fluoxetine experienced clinical benefit by lowering the risk of intubation and death. The aim of this study is to conduct population pharmacokinetic dosing simulations to quantify the percentage of patients achieving a trough level for the effective concentration resulting in 50% (EC50) and 90% (EC90) inhibition of SARS-CoV-2 as reported in Calu-3 human lung cells. Methods. Pharmacometric parameter estimates used in this study were obtained from the U.S. FDA website from a new drug application for fluoxetine hydrochloride. A population of 1,000 individuals were simulated at standard fluoxetine antidepressant doses (20 mg/day, 30 mg/day, 40 mg/day, 50 mg/day, and 60 mg/day) to estimate the percentage of the patients achieving a trough plasma level for the EC50 and EC90 SARS-CoV-2 inhibition. All analyses were conducted in R. Results. By day-10 at 20 mg/day, 93.2% and 47% of the population will achieve the trough target plasma EC50 and EC90 concentrations, respectively, which translates to a lung tissue distribution coefficient of 60-times higher EC50 (283.6 ng/ml [0.82 mM]) and EC90 (1390.1 ng/ml [4.02 mM]). Further, by day-10 at an ideal dose of 40 mg/day, 99% and 93% of patients will reach the trough EC50 and EC90 concentrations, respectfully. Lastly, only a dose of 60 mg/day will reach the SARS-CoV-2 EC90 inhibitory concentration in the brain at pharmacokinetic steady-state. Conclusion. Overall, with a minimum treatment period of 10-days and a minimum dose of 20 mg/day, this study corroborates in vitro studies reporting fluoxetine inhibiting SARS-CoV-2 titers and also multiple observational clinical studies showing therapeutic benefit of fluoxetine in COVID-19 patients.
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Eugene, Andy R. "Fluoxetine pharmacokinetics and tissue distribution quantitatively supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per day." F1000Research 10 (February 2, 2022): 477. http://dx.doi.org/10.12688/f1000research.53275.2.
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Background. Various in vitro studies have shown fluoxetine inhibits multiple variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen causing the coronavirus disease 2019 (COVID-19) worldwide pandemic and multiple observational clinical studies have shown that patients receiving fluoxetine experienced clinical benefit by lowering the risk of intubation and death. The aim of this study is to conduct population pharmacokinetic dosing simulations to quantify the percentage of patients achieving a trough level for the effective concentration resulting in 50% (EC50) and 90% (EC90) inhibition of SARS-CoV-2 as reported in Calu-3 human lung cells. Methods. Pharmacometric parameter estimates used in this study were obtained from the U.S. FDA website from a new drug application for fluoxetine hydrochloride. A population of 1,000 individuals were simulated at standard fluoxetine antidepressant doses (20 mg/day, 30 mg/day, 40 mg/day, 50 mg/day, and 60 mg/day) to estimate the percentage of the patients achieving a trough plasma level for the EC50 and EC90 SARS-CoV-2 inhibition. All analyses and graphing were conducted in R. Results. By day-10 at 20 mg/day 93.2% and 47% of the population will achieve the trough target plasma EC50 and EC90 concentrations, respectively, which translates to a lung tissue distribution coefficient of 60-times higher EC50 (283.6 ng/ml [0.82 mM]) and EC90 (1390.1 ng/ml [4.02 mM]). Further, by day-10 at an ideal dose of 40 mg/day, 99% and 93% of patients will reach the trough EC50 and EC90 concentrations, respectfully. Lastly, only a dose of 60 mg/day will reach the SARS-CoV-2 EC90 inhibitory concentration in the brain. Conclusion. Overall, with a minimum treatment period of 10-days and a minimum dose of 20 mg/day, this study corroborates in vitro studies reporting fluoxetine inhibiting SARS-CoV-2 titers and also multiple observational clinical studies showing therapeutic benefit of fluoxetine in COVID-19 patients.
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Neyts, J., and E. De Clercq. "Antiviral drug susceptibility of human herpesvirus 8." Antimicrobial Agents and Chemotherapy 41, no. 12 (1997): 2754–56. http://dx.doi.org/10.1128/aac.41.12.2754.
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We studied the susceptibility of human herpesvirus 8 (HHV-8) to a number of antiherpesvirus agents. The acyclic nucleoside phosphonate (ANP) analogs cidofovir and HPMPA [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine] effected potent inhibition of HHV-8 DNA synthesis, with 50% effective concentrations (EC50) of 6.3 and 0.6 microM, respectively. Adefovir, an ANP with both antiretrovirus and antiherpesvirus activity, blocked HHV-8 DNA replication at a fourfold-lower concentration than did foscarnet (EC50 of 39 and 177 microM, respectively). The most potent inhibitory effect was obtained with the N-7-substituted nucleoside analog S2242 (EC50, 0.11 microM). The nucleoside analogs acyclovir, penciclovir, H2G ((R)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine), and brivudine had weak to moderate effects (EC50 of > or =75, 43, 42, and 24 microM, respectively, and EC90 of > or =75 microM), whereas ganciclovir elicited pronounced anti-HHV-8 activity (EC50, 8.9 microM).
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Nigrovic, Vladimir. "Multiple Estimates of EC50." Anesthesiology 97, no. 1 (2002): 284. http://dx.doi.org/10.1097/00000542-200207000-00052.
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Varin, France. "Multiple Estimates of EC50." Anesthesiology 97, no. 1 (2002): 284. http://dx.doi.org/10.1097/00000542-200207000-00053.
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Chotivanich, Kesinee, Jetsumon Sattabongkot, Rachanee Udomsangpetch, et al. "Transmission-Blocking Activities of Quinine, Primaquine, and Artesunate." Antimicrobial Agents and Chemotherapy 50, no. 6 (2006): 1927–30. http://dx.doi.org/10.1128/aac.01472-05.
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ABSTRACT The infectivity of Plasmodium falciparum gametocytes after exposure in vitro to quinine, artesunate, and primaquine was assessed in Anopheles dirus, a major vector of malaria in Southeast Asia. Mature gametocytes (stage 5) of a Thai isolate of P. falciparum were exposed to the drugs for 24 h in vitro before membrane feeding to A. dirus. After 10 days, the mosquito midguts were dissected and the oocysts were counted. In this system, artesunate showed the most potent transmission-blocking activity; the mean (standard deviation [SD]) 50% and 90% effective concentrations (EC50, and EC90, respectively, in nanograms per milliliter) were 0.1 (0.02) and 0.4 (0.15), respectively. Transmission-blocking activity of quinine and primaquine was observed at relatively high concentrations (SDs): EC50 of quinine, 642 (111) ng/ml; EC50 of primaquine, 181 (23) ng/ml; EC90 of quinine, 816 (96) ng/ml; EC90 of primaquine, 543 (43) ng/ml. Artesunate both prevents the maturation of immature P. falciparum gametocytes and reduces the transmission potential of mature gametocytes. Both of these effects may contribute to reducing malaria transmission.
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Huebner, J. D., and K. S. Pynnönen. "Viability of glochidia of two species of Anodonta exposed to low pH and selected metals." Canadian Journal of Zoology 70, no. 12 (1992): 2348–55. http://dx.doi.org/10.1139/z92-315.
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Mature glochidia were stripped from the gills of gravid mussels and exposed to low pH (3 – 6.5), aluminum (150 – 3000 μg/L), aluminum (300 μg/L) at low pH (3–6.5), zinc (5 – 30 000 μg/L), cadmium (50–3000 μg/L), or copper (5 – 1500 μg/L) for 6 days. Viability was tested after 24, 48, 72, and 144 h by observing the ability of the glochidia to close when exposed to an irritant, 2.5 M KCl. Effective concentrations needed to reduce the closure response to 50% (EC50) under the experimental conditions were calculated using probit analysis. The relative toxicities (based on 48-h EC50s) of the metals to Anodonta cygnea glochidia were Cu (EC50 = 5.3 μg/L) > Cd (EC50 = 46.8 μg/L) > Zn (EC50 = 69.1 μg/L) > Al. The EC50 for pH was 4.34 for A. cygnea and 4.69 for Anodonta anatina. In 300 μg/L Al, the EC50 for pH for A. cygnea was 4.46. The ability of glochidia to close their valves is considered a reliable measure of viability, as this action is necessary for the larvae to complete the obligate ectoparasitic stage of their life cycle. Decrease in glochidial viability is suggested as a possible explanation for the disappearance of unionids from acid- and metal-contaminated waters.
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Parasramka, Mansi, David A. Proia, and Richard Wayne Joseph. "Preclinical activity of the heat shock protein 90 inhibitor ganetespib in clear cell renal cell carcinoma." Journal of Clinical Oncology 32, no. 4_suppl (2014): 478. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.478.
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478 Background: Resistance invariably develops in all patients with metastatic ccRCC treated with mTOR inhibitors. Previously we demonstrated that dual inhibition of Hsp90 and the mTOR pathway in lung cancer models leads to synergistic reductions in tumor growth. Herein, we tested the efficacy of ganetespib as a single agent and in combination with mTOR inhibition using in vitro and in vivoccRCC models. Methods: For the in vitro work we utilized the following seven ccRCC cell lines: Caki-1, Caki-2, A-498, A-704, 769-P, 786-O, ACHN. For the in vivo work we used A498 xenografts. In vitro, we determined the single agent EC50 of everolimus and ganetespib at 72 hours by assessing percent viability of A498 cells compared to vehicle using the MTS assay. We then performed combinations of ganetespib and everolimus at EC20, EC30, and EC50 in A498 cells. Translating these studies in vivo, we compared the combinatorial activity of ganetespib and temsirolimus to monotherapy in mice bearing A498 tumor xenografts. Results: As a single agent, all ccRCC cell lines tested were sensitive to ganetespib at nanomolar concentration (EC50 15 – 75 nm) and to everolimus at micromolar concentrations (EC50 4 – 54 mm). In vitro, the combination of ganetespib and everolimus also decreased cell viability in an additive fashion. In vivo, ganetespib and temsirolimus demonstrated comparable single agent activity at sub-MTD doses (T/C = 63 and 60, respectively). Combining ganetespib with temsirolimus improved tumor growth suppression by ~30% (T/C = 43). Conclusions: Given the broad in vitro sensitivity of ccRCC cell lines to single agent ganetespib as well as the in vivo activity of the combination of ganetespib and temsirolimus, we believe ganetespib warrants further study in ccRCC. Updated results will be presented at the conference including the in vivo activity of the combination of ganetespib and antivascular endothelial growth factor agents.
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Drusano, G. L., K. H. P. Moore, J. P. Kleim, W. Prince, and A. Bye. "Rational Dose Selection for a Nonnucleoside Reverse Transcriptase Inhibitor through Use of Population Pharmacokinetic Modeling and Monte Carlo Simulation." Antimicrobial Agents and Chemotherapy 46, no. 3 (2002): 913–16. http://dx.doi.org/10.1128/aac.46.3.913-916.2002.
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ABSTRACT In order to choose a rational dose for GW 420867X, we first set a goal of therapy. We hypothesized that, for optimal antiretroviral activity, the trough free drug concentration should remain above the 90% effective concentration (EC90) of human immunodeficiency virus type 1. We performed population pharmacokinetic analysis on three different doses of GW 420867X (50, 100, and 200 mg). Monte Carlo simulation was performed, assuming a log-normal distribution for 1,000 simulated subjects for each dose, and was repeated three times. The trough concentrations were divided by 76 to account for protein binding and for the difference between EC50 and EC90. We then determined the fraction of the simulated population whose free drug trough concentrations would exceed an EC90 over a broad range of values. The target attainment for all three doses exceeded 95% out to a starting EC50 of 10 nM. For 16 viral isolates, the EC50 range encountered for GW 420867X did not exceed 8 nM, implying that the three doses could not be differentiated by effect in a clinical trial in naive patients. This prediction was shown to be correct in a randomized, double-blind trial with 1 week of monotherapy with GW 420867X.
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Seifert, Karin, and Simon L. Croft. "In Vitro and In Vivo Interactions between Miltefosine and Other Antileishmanial Drugs." Antimicrobial Agents and Chemotherapy 50, no. 1 (2006): 73–79. http://dx.doi.org/10.1128/aac.50.1.73-79.2006.
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ABSTRACT The interaction of miltefosine with amphotericin B, sodium stibogluconate, paromomycin, and sitamaquine was assessed in vitro and additionally for the first three combinations in vivo. In vitro interactions were indifferent for miltefosine combined with amphotericin B (mean sums of fractional inhibitory concentrations [mean ∑FICs] ranging from 1.22 to 1.51 at the 50% effective concentration [EC50] level and 1.08 to 1.38 at the EC90 level), sitamaquine (mean ∑FICs from 1.33 to 1.38 and 1.0 to 1.02, respectively), and paromomycin (mean ∑FICs from 0.79 to 0.93 at the EC50 and 0.77 to 1.35 at the EC90 level). Some synergy was observed for miltefosine combined with sodium stibogluconate (mean ∑FICs from 0.61 to 0.75 at EC50 and 0.49 to 0.97 at EC90). Different interactions were found in vivo, where the highest potentiation of miltefosine activity was achieved with amphotericin B (activity enhancement index [AEI] of up to 11.3). No significant interaction was observed when miltefosine was combined with sodium stibogluconate (AEI of up to 2.38). The potentiation of miltefosine in vivo was also achieved with the combination of miltefosine and paromomycin (AEI of up to 7.22).
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Qiu, Y.-L., RG Ptak, JM Breitenbach, et al. "(Z)- and (E)-2-(Hydroxymethylcyclopropylidene)-Methylpurines and Pyrimidines as Antiviral Agents." Antiviral Chemistry and Chemotherapy 9, no. 4 (1998): 57–68. http://dx.doi.org/10.1177/095632029800900406.
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Several Z- and E-methylenecyclopropane nucleoside analogues were synthesized and evaluated for antiviral activity. Reaction of the Z- and E-2-amino-6-chloropurine methylenecyclopropanes with ammonia or cyclopropylamine gave 2,6-diamino or 2-amino-6-cyclopropylamino analogues. Alkylation elimination of N4-acetylcytosine with ethyl Z- and E-2-bromo-2-bromomethylcyclopropane-1-carboxylates gave a mixture of the Z-and E-methylenecyclopropane derivatives of cytosine. Reduction furnished a mixture of syncytol and the E isomer. Benzoylation led to the respective N4-benzoyl derivatives which were separated by chromatography. Debenzoylation afforded pure syncytol and the E isomer. Alkylation of 2,4-bis-O-trimethylsilylthymine with ethyl Z- and E-2-bromo-2-bromomethylcyclopropane-1-carboxylates gave the corresponding Z- and E-1-bromo-cyclopropylmethylderivatives of thymine. Base-catalysed elimination of HBr gave Z- and E-methylenecyclopropane carboxylic esters. Reduction furnished, after chromatographic separation, synthymol and the E isomer. The Z/E isomeric assignment of the obtained products followed from 1H NMR spectroscopy. The methylenecyclopropane analogues were tested for antiviral activity in vitro against human and murine cytomegalovirus (HCMV, MCMV), Epstein–Barr virus (EBV), varicella zoster virus (VZV), hepatitis B virus (HBV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpesvirus 6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1). The Z-2-amino-6-cyclopropylaminopurine analogue was the most effective agent against HCMV (EC50 or EC90 0.4–2 μM) followed by syncytol and the Z-2,6-diaminopurine analogues (EC50 or EC90 3.4–29 and 11–24 μM, respectively). The latter compound was also a strong inhibitor of MCMV (EC50 0.6 μM). Syncytol was the most potent against EBV (EC50 <0.41 and 2.5 μM) followed by the Z-2,6-diaminopurine (EC50 1.5 and 6.9 μM) and the Z-2-amino-6-cyclopropylaminopurine derivative (EC50 11.8 μM). Syncytol was also most effective against VZV (EC50 3.6 μM). Activity against HSV-1, HSV-2 and HHV-6 was generally lower; synthymol had an EC50 of 2 μM against HSV-1 (ELISA) and 1.3 μM against EBV in Daudi cells but was inactive in other assays. The 2-amino-6-cyclopropylamino analogue displayed EC50 values between 215 and >74 μM in HSV-1 and HSV-2 assays. 2-Amino-6-cyclopropylaminopurine and 2,6-diaminopurine derivatives were effective against HBV (EC50 2 and 10 μM, respectively), whereas none of the analogues inhibited HIV-1 at a higher virus load. Syncytol and the E isomer were equipotent against EBV in Daudi cells but the E isomer was much less effective in DNA hybridization assays. The E-2,6-diaminopurine analogue and E isomer of synthymol were devoid of antiviral activity.
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Su, Dan. "Biological Toxicity of Five Metal Ions on Marine Algea." Applied Mechanics and Materials 295-298 (February 2013): 17–20. http://dx.doi.org/10.4028/www.scientific.net/amm.295-298.17.
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Internationally validated methods (ISO standards) for the determination of toxic effects were used in this study to evaluate the toxicity of metals [i.e. Hg, Cu, Zn, Pb and Cd] to a kind of marine algae, namely Chlorella autotrophica. In the test, the no observable effect concentration (NOEC) and the effective concentration for 50% of test algae (EC50) were obtained after 96-h of incubation at 25±1°C, by comparing the growth of the Chlorella autotrophica in the test samples and in the control. Among the 5 metal ions, mercury (Hg) was found to be the most toxic metal in the test (EC50=1.04 mmol/L), while cadmium (Cd) was the least toxic (EC50=151.37 mmol/L). The results from the Chi-square test of each dose-response equations showed that 96h-EC50s calculated were all precise and credible. According to both NOEC and 96h-EC50, the toxic sequence of these metals from high to low on the inhibition of Chlorella autotrophica’s growth was Hg2+, Cu2+, Zn2+, Pb2+ and Cd2+.
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Kasi, Shaira R., Sanne Roffel, Mutlu Özcan, Susan Gibbs, and Albert J. Feilzer. "In vitro cytotoxicity (irritant potency) of toothpaste ingredients." PLOS ONE 20, no. 1 (2025): e0318565. https://doi.org/10.1371/journal.pone.0318565.
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Purpose This study aimed to determine the cytotoxicity (irritant potency) of toothpaste ingredients, of which some had known to have sensitizing properties. Materials From the wide variety of toothpaste ingredients, Xylitol, Propylene glycol (PEG), Sodium metaphosphate (SMP), Lemon, Peppermint, Fluoride, Cinnamon, and Triclosan and Sodium dodecyl sulphate (SDS) have been selected for evaluation of their cytotoxic properties. Methods Reconstructed human gingiva (RHG) were topically exposed to toothpaste ingredients at different concentrations. The compound concentration resulting in 50% cell death (EC50) and 10% cell death (EC10) was determined by the MTT assay. Detrimental effects in tissue histology were observed by hematoxylin & eosin staining of tissue sections followed by microscopy. Results While Xylitol, PEG, and SMP did not appear to affect cell viability or tissue histology, the concentrations of Lemon, Peppermint, Cinnamon and SDS present in toothpastes exceeded the EC50 value and resulted in clear detrimental effects in tissue histology, indicating that they could harm the oral mucosa. Triclosan and Fluoride concentrations in the tested toothpastes exceeded the EC10 value but remained below the EC50 value with no clear detrimental effects in tissue histology. Clinical significance Manufacturers are encouraged to comply with higher standards of quality and safety for toothpaste.
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Salam, Alex P., Alexandre Duvignaud, Marie Jaspard, et al. "Ribavirin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing." PLOS Neglected Tropical Diseases 16, no. 3 (2022): e0010289. http://dx.doi.org/10.1371/journal.pntd.0010289.
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Ribavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 μg/ml to 21.72 μg/ml and the EC90 ranged from 1.5 μg/ml to 29 μg/ml. The mean EC50 was 7 μg/ml and the mean EC90 was 15 μg/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharmacokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the possibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever.
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Kerdoun, Rym Messaouda, Mohamed Amine Kerdoun, Laid Touati, and Hakim Belkhalfa. "Sensitivity of Daphnia magna: Acute Toxicity Evaluation of 22 Metals." Journal of Pharmacy and Nutrition Sciences 14 (October 29, 2024): 62–70. http://dx.doi.org/10.29169/1927-5951.2024.14.08.
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Introduction: All potentially toxic metals in the environment can be discharged in the aquatic ecosystems. Daphnia magna is one of the most sensitive species to toxic chemicals in water and is frequently used in toxicological research and environmental monitoring. Material and Methods: Acute toxicity test for twenty-two metals (Pb, Cd, Ni, Hg, Cu, Fe, Co, As, Cr, Mn, Zn, Al, Pd, Na, K, Mo, Mg, Ca, W, Ir, Ti, Ag) was carried out for Daphnia magna. These elements were checked and ranked in terms of decreased immobilization (EC50) after 24Hr and 48Hr and compared with previous studies. Results: The results were categorized into four groups by the 48Hr EC50s values: highly toxic groups (Ag, Hg, Cu, Cd, Pd) [EC50 < 100 μg.l-1], moderately toxics groups Cr, Fe, Ni, Zn and Pb) [100 μg.l-1<EC50 < 1 000 μg.l-1], low toxic groups (Al, Mn, As, Ti, Co, W and Ir) [1000 μg.l-1<EC50 < 100000 μg.l-1], and minimally toxic groups (Na, Mg, K, Ca, and Mo) [EC50 > 100 000 μg.l-1]. Correlation coefficients (r) between EC values and eight physicochemical properties were also examined. The results obtained in this study were weak. Conclusion: This work adds and confirm data about the toxicities of metals in aquatic ecosystems by using a rapid biomonitoring test.
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Mina BOUHALLAOUI, Bouchra ELHAIMEUR, Hamza BENRAHMA, and Ali BENHRA. "Use of bacterial bioluminescence (Microtox test) as a tool for assessing the toxicity of pure substances and complex effluents (Moroccan Atlantic coast)." Global Journal of Engineering and Technology Advances 22, no. 1 (2025): 046–55. https://doi.org/10.30574/gjeta.2025.22.1.0252.
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The Microtox test is a rapid, simple, and widely used test in the context of screening and comparative studies. The aim of this study is to use the Vibrio fischeri bacteria luminescence inhibition test to assess the toxicity of metals and those of industrial unit discharges. The assessment of the effects of discharges on V. fischeri luminescence reveals the great sensitivity of this bioindicator to discharges and highlights a high risk of deterioration in the quality of the marine environment, particularly in the areas where discharges, with EC50s which can reach 0.25% discharge into the test medium for petrochemical effluents after 5 minutes of exposure. The analysis of these results made it possible to classify the discharges according to their toxicity towards the bacterium V. fischeri and to draw up a profile of the impact of these discharges according to the EC50 values. The results of tests carried out on metals show that mercury is the most toxic metal (EC50 = 0.63 mg Hg L-1), followed by lead (EC50 = 1.08 mg Pb L-1) and cadmium (EC50 = 1.87 mg Cd L-1) and finally copper (EC50 = 2.57 mg Cu L-1). The results obtained during this study show that the Microtox test represents a good model for evaluating the toxicity of complex discharges and pure substances and that bacterial luminescence constitutes an excellent bioindicator for screening the medium quality.
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Borgmann, U., W. P. Norwood, and I. M. Babirad. "Relationship between Chronic Toxicity and Bioaccumulation of Cadmium in Hyalella azteca." Canadian Journal of Fisheries and Aquatic Sciences 48, no. 6 (1991): 1055–60. http://dx.doi.org/10.1139/f91-124.
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The chronic toxicity of Cd to Hyalella in Burlington City tap (Lake Ontario) water with additions of complexing agents, distilled water, or sediments was much more constant if toxicity was expressed as a function of Cd bioaccumulated, rather than the Cd concentrations added or measured in the water. Additions of 20 mg humic acid/L or 0.5 μM EDTA increased the 6-wk EC50 from 0.53 to 4.6 and 19 μg/L, respectively. The EC50 based on bioaccumulated Cd, however, increased from 38 to only 44 μg/g (dry weight). Addition of sediments increased the 4-wk EC50 by > 1000-, 13-, or 2.3-fold for EC50s based on nominal Cd added, Cd concentrations measured in water, or Cd concentrations accumulated by Hyalella, respectively. A 10-fold reduction in hardness caused a twofold increase in the 6-wk EC50 based on Cd accumulation. The relationship between survival and Cd bioaccumulation by Hyalella was, therefore, affected less by complexing agents, hardness, and sediments than was survival compared with concentrations in water. Published Cd concentrations in Hyalella from a number of Ontario lakes are close to levels associated with toxicity in the laboratory.
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Klepser, Michael E., Dennis Malone, Russell E. Lewis, Erika J. Ernst, and Michael A. Pfaller. "Evaluation of Voriconazole Pharmacodynamics Using Time-Kill Methodology." Antimicrobial Agents and Chemotherapy 44, no. 7 (2000): 1917–20. http://dx.doi.org/10.1128/aac.44.7.1917-1920.2000.
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ABSTRACT Voriconazole is an investigational azole antifungal agent with activity against a variety of fungal species, including fluconazole-susceptible and -resistant Candida species andCryptococcus neoformans. In this study, we employed in vitro time-kill methods to characterize the relationship between concentrations of voriconazole and its fungistatic activity againstCandida albicans, Candida glabrata,Candida tropicalis, and C. neoformans. Isolates were exposed to voriconazole concentrations ranging from 0.0625 to 16 times the MIC, and the viable colony counts were determined over time. The 50 and 90% effective concentrations (EC50 and EC90, respectively) were determined at 8, 12, and 24 h following the addition of voriconazole. At each time point, near-maximal fungistatic activity, as indicated by the EC90, was noted at a drug concentration of approximately three times the MIC. Additionally, EC50 and EC90 did not change over time, thus suggesting that the rate of activity was not improved by increasing concentrations. Voriconazole exhibits non-concentration-dependent pharmacodynamic characteristics in vitro.
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Tonner, Peter H., Jeans Scholz, Lars Lamberz, Nikolas Schlamp, and Jochen Schulte am Esch. "Inhibition of Nitric Oxide Synthase Decreases Anesthetic Requirements of Intravenous Anesthetics in Xenopus laevis." Anesthesiology 87, no. 6 (1997): 1479–85. http://dx.doi.org/10.1097/00000542-199712000-00027.
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Background Acute inhibition of nitric oxide synthase (NOS) has been demonstrated to reduce the anesthetic requirements of volatile anesthetics. Recent data suggest that not only volatile but also intravenous anesthetic agents interact with nitric oxide (NO) metabolism. The aim of this study was to examine the effect of NOS inhibition by nitroG-L-arginine-methyl-ester (L-NAME) on the anesthetic action of the intravenous anesthetics thiopental, propofol, and ketamine. Methods The anesthetic potencies of thiopental, propofol, and ketamine were determined in Xenopus laevis tadpoles in the absence and presence of L-NAME. Anesthesia was defined as loss of righting reflex for 5 s. A nonlinear logistic regression curve was fitted to the data and half-maximal effective concentrations (EC50) were calculated. A second set of experiments was performed with different concentrations of L-NAME in the presence of the previously determined the EC50 of the intravenous anesthetics. Results The EC50s of the anesthetics thiopental, propofol, and ketamine were determined to be 25.5 +/- 2.0 microM, 1.9 +/- 0.1 microM, and 59.7 +/- 0.7 microM, respectively. The addition of L-NAME shifted the concentration-response curves to the left in a concentration-dependent manner. In the presence of 1 mM L-NAME, the EC50 of thiopental was reduced by 43%, the EC50 of propofol by 26%, and the EC50 of ketamine by 63%. The addition of D-NAME did not change the EC50 values of the three anesthetics. In the presence of L-arginine, the effect of L-NAME on the EC50 of thiopental was reversed. When administered by itself in a concentration range from 0.1 microM to 10 mM, L-NAME did not alter the behavior of the tadpoles. Conclusions The results of the present study show that acute inhibition of NOS by L-NAME results in reduced anesthetic requirements of the intravenous anesthetics thiopental, propofol, and ketamine. This interaction of acutely administered L-NAME and intravenous anesthetics indicates that the NO-cyclic guanosine 3',5'-monophosphate system is involved in mediating the anesthetic effect of these compounds.
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Sebaugh, J. L. "Guidelines for accurate EC50/IC50 estimation." Pharmaceutical Statistics 10, no. 2 (2011): 128–34. http://dx.doi.org/10.1002/pst.426.
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Yedidi, Ravikiran S., Harisha Garimella, Manabu Aoki, et al. "A Conserved Hydrogen-Bonding Network of P2bis-Tetrahydrofuran-Containing HIV-1 Protease Inhibitors (PIs) with a Protease Active-Site Amino Acid Backbone Aids in Their Activity against PI-Resistant HIV." Antimicrobial Agents and Chemotherapy 58, no. 7 (2014): 3679–88. http://dx.doi.org/10.1128/aac.00107-14.
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ABSTRACTIn the present study, GRL008, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), and darunavir (DRV), both of which contain a P2-bis-tetrahydrofuranyl urethane (bis-THF) moiety, were found to exert potent antiviral activity (50% effective concentrations [EC50s], 0.029 and 0.002 μM, respectively) against a multidrug-resistant clinical isolate of HIV-1 (HIVA02) compared to ritonavir (RTV; EC50, >1.0 μM) and tipranavir (TPV; EC50, 0.364 μM). Additionally, GRL008 showed potent antiviral activity against an HIV-1 variant selected in the presence of DRV over 20 passages (HIVDRVRP20), with a 2.6-fold increase in its EC50(0.097 μM) compared to its corresponding EC50(0.038 μM) against wild-type HIV-1NL4-3(HIVWT). Based on X-ray crystallographic analysis, both GRL008 and DRV showed strong hydrogen bonds (H-bonds) with the backbone-amide nitrogen/carbonyl oxygen atoms of conserved active-site amino acids G27, D29, D30, and D30′ of HIVA02protease (PRA02) and wild-type PR in their corresponding crystal structures, while TPV lacked H-bonds with G27 and D30′ due to an absence of polar groups. The P2′ thiazolyl moiety of RTV showed two conformations in the crystal structure of the PRA02-RTV complex, one of which showed loss of contacts in the S2′ binding pocket of PRA02, supporting RTV's compromised antiviral activity (EC50, >1 μM). Thus, the conserved H-bonding network of P2-bis-THF-containing GRL008 with the backbone of G27, D29, D30, and D30′ most likely contributes to its persistently greater antiviral activity against HIVWT, HIVA02, and HIVDRVRP20.
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Cova, Dario, Pietro Fumagalli, and Angela Santagostino. "Toxicity of Ethylene-bis-dithiocarbamates (EBDCs) in a Human Neuroblastoma Cell Line." Alternatives to Laboratory Animals 19, no. 1 (1991): 39–40. http://dx.doi.org/10.1177/026119299101900108.
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The aim of our research was the in vitro evaluation of the neurotoxic effects of three EBDCs (Nabam, Zineb and Maneb) and ETU on SK-N-BE human neuroblastoma cells as a model for neurotoxicity in humans. The EC50 value was used as an index of the toxicities of these compounds. Since Zineb and Maneb contain zinc and manganese as cations, respectively, in order to determine the contributions of these metals, the EC50s of zinc chloride and manganese chloride were also evaluated. Nabam, Zineb and Maneb had EC50 values ranging from 1μM to 30μM; the EC50s of manganese and zinc in this human cell line were found to be of the same order of magnitude as those of the EBDC fungicides. These in vitro effects are discussed in relation to the possible use of neuronal cell lines for detecting the neurotoxicities of these compounds.
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Siciliano, Antonietta, Marisa Spampinato, Giovanna Salbitani, et al. "Multi-Endpoint Analysis of Cerium and Gadolinium Effects after Long-Term Exposure to Phaeodactylum tricornutum." Environments 11, no. 3 (2024): 58. http://dx.doi.org/10.3390/environments11030058.
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The significantly increasing levels of Rare Earth Elements (REEs) in seawater are largely due to multiple anthropogenic activities. Their effects on marine primary producers such as Phaeodactylum tricornutum have not been fully assessed. This study focused on examining the long-term impacts of these two commonly occurring REEs, cerium (Ce) and gadolinium (Gd), on marine diatoms by 28 d of exposure. The 72 h effective concentrations that inhibited the growth of 20% (EC20) and 50% (EC50) of the exposed population were used for long-term exposures. The growth, oxidative stress level, photosynthetic pigments, and chlorophyll fluorescence were assessed in the diatoms, after 7, 14, 21, and 28 d of REEs exposure. Results display a difference in the toxicity induced by the two elements. Exposure to 2.39 mg/L (EC20) and 3.13 mg/L (EC50) of Ce, and to 4.52 mg/L (EC20) and 6.02 mg/L (EC50) of Gd displayed a lower effect on the growth of algae cells, as the response remained below 20% for inhibition or stimulation. Except for GD, the ROS and the activities of SOD, and LPO showed, during the exposure, comparable levels respect to control cells. A change in chlorophyll levels was also observed especially under Ce exposure. Both elements showed changes in photosynthetic performance. This study provides new insights into the different effects of Ce and Gd on P. tricornutum, demonstrating their diverse modes of action on this important primary producer. The findings provide further evidence of the adverse effects of anthropogenic REEs pollution on marine ecosystems.
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Cabrera, J. Alfonso, Sebastian Kiewnick, Christoph Grimm, Abd el-Fattah A. Dababat, and Richard A. Sikora. "Effective concentration and range of activity of abamectin as seed treatment against root-knot nematodes in tomato under glasshouse conditions." Nematology 11, no. 6 (2009): 909–15. http://dx.doi.org/10.1163/156854109x433371.
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Abstract The objectives of this study were to determine the efficacy, range of activity and effective concentrations (EC50 and EC80) of abamectin as a seed treatment of tomato against Meloidogyne incognita, M. arenaria and M. javanica. The study revealed that abamectin seed treatment at concentrations ranging between 0.3 and 1 mg a.s. seed−1 is highly effective against the three species of root-knot nematodes, retaining its efficacy in the soil for 8 weeks. The highest EC50 found was reached at 0.2 mg a.s. seed−1. The highest EC80 for the number of egg masses per g root in the three Meloidogyne species was attained at 0.51 mg a.s. seed−1. Abamectin as a seed treatment is promising for the control of root-knot nematodes in the field since only low amounts of active ingredient are required to give adequate protection in the most sensitive stages of tomato root growth and development.
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Singh, Ramendra K., Agnieszka Miazga, Aleksandra Dąbrowska, et al. "Myristoylated Derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine) bi-Functional Prodrugs with Potent Anti-HIV-1 Activity and Low Cytotoxicity." Antiviral Chemistry and Chemotherapy 23, no. 6 (2014): 231–35. http://dx.doi.org/10.3851/imp2679.
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Background: To improve in vitro antiviral activity and selectivity of stavudine (d4T), a range of its bi-functional prodrugs, 5′- O-myristoylated derivatives, have been synthesized. Methods: Stavudine 5′- O-myristoylated esters were synthesized using modified Parang's procedure. The cytotoxicity and anti-HIV activity was evaluated in the established MT-4 cell line. The level of p24 protein in culture medium was assayed, and EC50 and EC90 values were determined. Results: Excellent anti-HIV activity was obtained for stavudine derivatives 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(11-thioethylundecanoyl) thymidine, 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(12-thioethyldodecanoyl) thymidine and 5′- O-(12-azidododecanoyl)-2′,3′-didehydro-2′,3′-dideoxythymidine with C10 and C11 alkyl chains bearing thioethyl- and azido- substituents. These prodrugs were more potent than the parent stavudine, as is clear from their EC50 values: 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(11-thioethylundecanoyl) thymidine (R=CO(CH2)10SC2H5, EC50 0.06 μM), 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(12-thioethyldodecanoyl) thymidine (R=CO(CH2)11SC2H5, EC50 0.09 μM) and 5′- O-(12-azidododecanoyl)-2′,3′-didehydro-2′,3′-dideoxythymidine (R=CO(CH2)11N3, EC50 0.06 μM), while 50% cytotoxic concentration was >16.65 μM, >7.5 μM and >18.53 μM, respectively. Conclusions: Overall data demonstrate that compounds 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(11-thioethylundecanoyl) thymidine, 2′,3′-didehydro-2′,3′-dideoxy-5′- O-(12-thioethyldodecanoyl) thymidine and 5′- O-(12-azidododecanoyl)-2′,3′-didehydro-2′,3′-dideoxythymidine are very potent and selective anti-HIV agents and could be useful in treatment of HIV infections of the central nervous system.
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Moghaddam, Razieh Afshar, Farahnaz Jazaeri, Alireza Abdollahi, Razieh Mohammadjafari, Ahmad Reza Dehpour, and Azam Bakhtiarian. "Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats." Drug Research 69, no. 06 (2018): 352–60. http://dx.doi.org/10.1055/a-0800-8391.
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AbstractThe main vascular feature in endotoxemia is impaired contractile responses to vasoactive agents. We study the aortic response to 5HT11 A, 5HT1B1D and 5HT2A receptors agonist and antagonist in chronic endotoxemic rats. Intraperitoneal injection of 1 mg/kg lipopolysaccharide for 5 days induced chronic endotoxemia. Control rats received intraperitoneal injection of 1 ml/kg saline for 5 days. Rats divided into 3 groups. In first, DOI2 hydrochloride used as an agonist and sarpogrelate hydrochloride as an antagonist of 5HT2A receptor. In second, (R)-(+)-8-OH-DPAT3 and WAY1001354 used as an agonist and antagonist of 5HT1A receptor respectively. In third, Zolmitriptan used as an agonist and GR127935 hydrochloride as an antagonist of 5HT1B1D receptor. Aorta Isolated for organ bath study. Real time-PCR5 and histopathological study examined receptors gene expression and protein localization. Cumulative 8-OH-DPAT caused relaxation in control aorta (EC506 7.79±21.35 and 8.53±10.74 with and without antagonist), which was enhanced in endotoxemia (EC50 6.35±8.48 and very wide±17.38 with and without antagonist). Cumulative zolmitriptan caused relaxation in control aorta (EC50 very wide±8.65 and 8.38±8.44 with and without antagonist), which was enhanced in endotoxemia (EC50 very wide±9.53 and 8.37±13.49 with and without antagonist). DOI hydrochloride contracted the control aorta (EC50 6.51±7.14 and 5.98±1.65 with and without antagonist), which was converted to relaxation in endotoxemic group (EC50 infinity±80.43 and 7.37±20.28 with and without antagonist). PCR studies revealed enhanced 5HT1A receptor and diminished 5HT1B1D and 5HT2A receptor genes expression, while histopathological studies showed inflamed, damaged endothelium in endotoxemic aorta. Our data supports enhanced vasodilation and impaired vasoconstriction during endotoxemia.
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Todorovic, Slobodan M., and Christopher J. Lingle. "Pharmacological Properties of T-Type Ca2+ Current in Adult Rat Sensory Neurons: Effects of Anticonvulsant and Anesthetic Agents." Journal of Neurophysiology 79, no. 1 (1998): 240–52. http://dx.doi.org/10.1152/jn.1998.79.1.240.
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Todorovic, Slobodan M. and Christopher J. Lingle. Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents. J. Neurophysiol. 79: 240–252, 1998. We have used the whole cell patch-clamp method to study pharmacological properties of low-voltage–activated (LVA) Ca2+ current in freshly dissociated neurons from dorsal root ganglia of adult rats. Inward barium current [in the presence of internal fluoride to reduce L-type high-voltage–activated (HVA) and external 1 μM ω-conotoxin GVIA to blockN-type HVA current] was evoked from negative holding potentials of −90 mV to test potentials of −25 mV and showed complete inactivation during 200-ms test pulses. Amiloride blocked ∼90% of current with half-maximal block (EC50) of 75 μM and a Hill coefficient ( n) of 0.99. LVA current was blocked completely by inorganic Ca2+ channel blockers: lanthanum (EC50 = 0.53 μM) > zinc (EC50 = 11.3 μM) > cadmium (EC50 = 20 μM)> nickel (EC50 = 51 μM). The antiepileptics, ethosuximide (EC50 = 23.7 mM, n = 1.4), phenytoin (EC50 = 7.3 μM, n = 1.3), α-methyl-α-phenylsuccinimide (EC50 = 170 μM, n = 2.1), and valproic acid (EC50 = 330 μM, n = 1.9) maximally blocked ∼100, 60, 26, and 17% of T current, respectively. Another antiepileptic, carbamazepine (≤100 μM), and convulsants such as pentylenetetrazole (1 mM) and tert-butyl-bicyclo [2.2.2] phosphorothionate (50 μM) had no effect on T current. Barbiturates completely blocked T current: thiopental (EC50 = 153 μM, n =1.2) > pentobarbital (EC50 = 334 μM, n = 1.2) > methohexital (EC50 = 502 μM, n = 1.3) > phenobarbital (EC50 = 1.7 mM, n = 1.2). Blockade by thiopental and pentobarbital did not show voltage or use dependence. General anesthetics blocked T current completely and reversibly: propofol (EC50 = 12.9 μM, n = 1.3) > octanol(EC50 = 122 μM, n = 1.2) > etomidate (EC50 = 205 μM, n =1.3) > isoflurane (EC50 = 303 μM, n = 2.3) > halothane (EC50 = 655 μM, n = 2.0) > ketamine (EC50 = 2.5 mM, n = 1.1). Mibefradil, a novel Ca2+ channel blocker, blocked dorsal root ganglion T current in a voltage- and use-dependent fashion with an EC50 of ∼3 μM( n = 1.3). When compared with results on other T currents, these data indicate that significant differences exist among different T currents in terms of pharmacological sensitivities. Furthermore, differences in pharmacological sensitivity of T currents among peripheral neurons, CNS, and neuroendocrine cells may contribute to the spectrum of effects of particular analgesic, anticonvulsant, and anesthetic drugs.
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Singh, G., P. J. Rup, and Opender Koul. "Acute, sublethal and combination effects of azadirachtin and Bacillus thuringiensis toxins on Helicoverpa armigera (Lepidoptera: Noctuidae) larvae." Bulletin of Entomological Research 97, no. 4 (2007): 351–57. http://dx.doi.org/10.1017/s0007485307005019.
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AbstractThe efficacy of neem (1500 ppm azadirachtin (AI)), Delfin®WG™, a biological insecticide based on selected strain of Bacillus thuringiensis Berliner (Bt) subspecies kurstaki, and Cry1Ac protein, either individually or in combination, were examined against first to fourth instar Helicoverpa armigera (Hübner) larvae. Using an oral administration method, various growth inhibitory concentrations (EC) and lethal concentrations (LC) were determined for each bioagent. Combinations of sublethal concentrations of Bt spray formulation with azadirachtin at EC50 or EC95 levels not only enhanced the toxicity, but also reduced the duration of action when used in a mixture. The LC20 and LC50 values for Cry1Ac toxin were 0.06 and 0.22 μg ml−1, respectively. Bt–azadirachtin combinations of LC50+EC20 and LC50+EC50 result in 100% mortality. The mortality also was significant in LC20+EC20 and LC20+EC50 mixtures. These studies imply that the combined action is not synergistic but complimentary, with azadirachtin particularly facilitating the action of Bt. The Bt spray–azadirachtin combination is more economical than combinations that involve isolating the toxic protein, as the Bt spray formulations can be combined in a spray mixture with neem. These combinations may be useful for controlling bollworm populations that have acquired resistance to Bt as they may not survive the effect of mixture. Azadirachtin may be useful as a means of reducing the endotoxin concentrations in a mixture, to promote increased economic savings and further reduce the probability of resistance development to either insect control agent.
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Akkarawongsa, Radeekorn, Nina E. Pocaro, Gary Case, Aaron W. Kolb, and Curtis R. Brandt. "Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection." Antimicrobial Agents and Chemotherapy 53, no. 3 (2008): 987–96. http://dx.doi.org/10.1128/aac.00793-08.
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ABSTRACT The 773-residue ectodomain of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) has been resistant to the use of mutagenic strategies because the majority of the induced mutations result in defective proteins. As an alternative strategy for the identification of functionally important regions and novel inhibitors of infection, we prepared a library of overlapping peptides homologous to the ectodomain of gB and screened for the ability of the peptides to block infection. Seven of 138 15-mer peptides inhibited infection by more than 50% at a concentration of 100 μM. Three peptides (gB94, gB122, and gB131) with 50% effective concentrations (EC50s) below 20 μM were selected for further studies. The gB131 peptide (residues 681 to 695 in HSV-1 gB [gB-1]) was a specific entry inhibitor (EC50, ∼12 μM). The gB122 peptide (residues 636 to 650 in gB-1) blocked viral entry (EC50, ∼18 μM), protected cells from infection (EC50, ∼72 μM), and inactivated virions in solution (EC50, ∼138 μM). We were unable to discern the step or steps inhibited by the gB94 peptide, which is homologous to residues 496 to 510 in gB-1. Substitution of a tyrosine in the gB122 peptide (Y640 in full-length gB-1) reduced the antiviral activity eightfold, suggesting that this residue is critical for inhibition. This peptide-based strategy could lead to the identification of functionally important regions of gB or other membrane proteins and identify novel inhibitors of HSV-1 entry.
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Preston, Sandra L., Peter J. Piliero, John A. Bilello, Daniel S. Stein, William T. Symonds, and George L. Drusano. "In Vitro-In Vivo Model for Evaluating the Antiviral Activity of Amprenavir in Combination with Ritonavir Administered at 600 and 100 Milligrams, Respectively, Every 12 Hours." Antimicrobial Agents and Chemotherapy 47, no. 11 (2003): 3393–99. http://dx.doi.org/10.1128/aac.47.11.3393-3399.2003.
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ABSTRACT The study objective was to evaluate the pharmacodynamics of amprenavir in an in vitro system, develop an exposure target for maximal viral suppression, and determine the likelihood of target attainment based on the pharmacokinetics of amprenavir and ritonavir in human immunodeficiency virus (HIV)-infected patients. Population pharmacokinetic data were obtained from 13 HIV-infected patients receiving amprenavir and ritonavir in doses of 600 and 100 mg, respectively, every 12 h. A 2,500-subject Monte Carlo simulation was performed. Target attainment was also estimated for a target derived from clinical data. Maximal viral suppression (in vitro) was achieved when amprenavir free-drug concentrations remained greater than four times the 50% effective concentration (EC50) for 80% of the dosing interval. At an amprenavir EC50 of 0.03 μM, the likelihood of target attainment is 97.4%. For reduced-susceptibility isolates for which the EC50s are 0.05 and 0.08 μM, target attainment is 91.0 and 75.8%, respectively. For the clinical target of a trough concentration/EC50 ratio of 5, the target attainment rates were similar. Treatment with amprenavir and ritonavir at doses of 600 and 100 mg, respectively, twice a day provides excellent suppression of wild-type isolates and reduced-susceptibility isolates up to an EC50 of 0.05 μM. Even at 0.12 μM, target attainment likelihood exceeds 50%, making this an option for patients with extensive exposure to protease inhibitors when this treatment is used with additional active antiretroviral agents.
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Yang, X. J., L. J. Yang, F. S. Zeng, et al. "Distribution of Baseline Sensitivities to Natural Product Physcion Among Isolates of Sphaerotheca fuliginea and Pseudoperonospora cubensis." Plant Disease 92, no. 10 (2008): 1451–55. http://dx.doi.org/10.1094/pdis-92-10-1451.
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The ethanol extract from rhubarb was commercialized in China (Veguard, Physcion, 5 g/liter AS) for control of cucumber powdery mildew (Sphaerotheca fuliginea) and cucumber downy mildew (Pseudoperonospora cubensis). To provide the basic data for the risk assessment of resistance to this product, physcion was selected to represent the active ingredients to establish baseline sensitivity of powdery mildew and downy mildew populations. For powdery mildew, 262 isolates of S. fuliginea from nine regions and, for downy mildew populations, 116 isolates of P. cubensis from six regions were collected in China during 2004 and 2005 and tested for sensitivity. In addition, the sensitivity of a powdery mildew isolate was monitored for 15 asexual generations under selection pressure with physcion. The results showed that there was no significant difference among regions in the frequency distribution of baseline sensitivity to this ingredient for either cucumber powdery mildew isolates or cucumber downy mildew isolates. Baseline sensitivity was distributed as a normal unimodal curve with a mean median (50%) effective concentration (EC50) of 0.304 μg/ml for powdery mildew population and mean EC50 of 0.501 μg/ml for downy mildew population. The variation of sensitivity to physcion was low because the range factor (maximum EC50/minimum EC50 of isolates within population) varied from 1.63 to 3.42 among powdery mildew populations and from 1.70 to 2.38 among downy mildew populations. The powdery mildew isolate XZ4 did not decrease sensitivity under the selection pressure of physcion at the dose of EC70 for 15 generations.
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Bolton, Melvin D., Viviana Rivera-Varas, Luis E. del Río Mendoza, Mohamed F. R. Khan, and Gary A. Secor. "Efficacy of Variable Tetraconazole Rates Against Cercospora beticola Isolates with Differing In Vitro Sensitivities to DMI Fungicides." Plant Disease 96, no. 12 (2012): 1749–56. http://dx.doi.org/10.1094/pdis-03-12-0255-re.
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Cercospora leaf spot (CLS) of sugar beet is caused by the fungus Cercospora beticola. CLS management practices include the application of the sterol demethylation inhibitor (DMI) fungicides tetraconazole, difenoconazole, and prothioconazole. Evaluating resistance to DMIs is a major focus for CLS fungicide resistance management. Isolates were collected in 1997 and 1998 (baseline sensitivity to tetraconazole, prothioconazole, or difenoconazole) and 2007 through 2010 from the major sugar-beet-growing regions of Minnesota and North Dakota and assessed for in vitro sensitivity to two or three DMI fungicides. Most (47%) isolates collected in 1997–98 exhibited 50% effective concentration (EC50) values for tetraconazole of <0.01 μg ml–1, whereas no isolates could be found in this EC50 range in 2010. Since 2007, annual median and mean tetraconazole EC50 values have generally been increasing, and the frequency of isolates with EC50 values >0.11 μg ml–1 increased from 2008 to 2010. In contrast, the frequency of isolates with EC50 values for prothioconazole of >1.0 μg ml–1 has been decreasing since 2007. Annual median difenoconazole EC50 values appears to be stable, although annual mean EC50 values generally have been increasing for this fungicide. Although EC50 values are important for gauging fungicide sensitivity trends, a rigorous comparison of the relationship between in vitro EC50 values and loss of fungicide efficacy in planta has not been conducted for C. beticola. To explore this, 12 isolates exhibiting a wide range of tetraconazole EC50 values were inoculated to sugar beet but no tetraconazole was applied. No relationship was found between isolate EC50 value and disease severity. To assess whether EC50 values are related to fungicide efficacy in planta, sugar beet plants were sprayed with various dilutions of Eminent, the commercial formulation of tetraconazole, and subsequently inoculated with isolates that exhibited very low, medium, or high tetraconazole EC50 values. The high EC50 isolate caused significantly more disease than isolates with medium or very low EC50 values at the field application rate and most reduced rates. Because in vitro sensitivity testing is typically carried out with the active ingredient of the commercial fungicide, we investigated whether loss of disease control was the same for tetraconazole as for the commercial product Eminent. The high EC50 isolate caused more disease on plants treated with tetraconazole than Eminent but disease severity was not different between plants inoculated with the very low EC50 isolate.
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Ku, T. H., C. F. Ken, S. F. Yang, Y. M. Tsao, G. S. Chen, and C. Y. Tang. "Isoflurane anesthesia EC50 and LC50 for zebrafish." European Journal of Anaesthesiology 30 (June 2013): 153–54. http://dx.doi.org/10.1097/00003643-201306001-00478.
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Chen, H. F., and S. S. Q. Hee. "Ketone EC50 Values in the Microtox Test." Ecotoxicology and Environmental Safety 30, no. 2 (1995): 120–23. http://dx.doi.org/10.1006/eesa.1995.1014.
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Sponer, Ulrike, Somsak Prajakwong, Gerhard Wiedermann, Herwig Kollaritsch, Gunther Wernsdorfer, and Walther H. Wernsdorfer. "Pharmacodynamic Interaction of Doxycycline and Artemisinin in Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 46, no. 1 (2002): 262–64. http://dx.doi.org/10.1128/aac.46.1.262-264.2002.
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ABSTRACT Parallel in vitro tests, assessing the inhibition of schizont maturation, were conducted with 31 fresh isolates of Plasmodium falciparum from Thailand, using artemisinin, doxycycline, and combinations of both. The activities of artemisinin and doxycycline are obviously not correlated. Both compounds showed consistent synergism at 50% effective concentration (EC50), EC90, and EC99 levels.
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Ramharter, M., H. Noedl, H. Winkler, et al. "In Vitro Activity and Interaction of Clindamycin Combined with Dihydroartemisinin against Plasmodium falciparum." Antimicrobial Agents and Chemotherapy 47, no. 11 (2003): 3494–99. http://dx.doi.org/10.1128/aac.47.11.3494-3499.2003.
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ABSTRACT Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC50) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC50 and EC90 levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.
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Badawy, Mohamed E. I., and Entsar I. Rabea. "Synthesis and Antimicrobial Activity of N-(6-Carboxyl Cyclohex-3-ene Carbonyl) Chitosan with Different Degrees of Substitution." International Journal of Carbohydrate Chemistry 2016 (October 23, 2016): 1–10. http://dx.doi.org/10.1155/2016/6046232.
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Five products of N-(6-carboxyl cyclohex-3-ene carbonyl) chitosan as antimicrobial agents were prepared by reaction of chitosan with tetrahydrophthalic anhydride (THPA) at different degrees of substitution (DS). The antimicrobial activity was evaluated against four plant bacteria and eight fungi. The results proved that the inhibitory property and water solubility of the synthesized chitosan derivatives, with increase of the DS, exhibited a remarkable improvement over chitosan. The product with a DS of 0.40 was the most active one with MIC of 510, 735, 240, and 385 mg/L against Erwinia carotovora, Ralstonia solanacearum, Rhodococcus fascians, and Rhizobium radiobacter, respectively, and also in mycelial growth inhibition against Alternaria alternata (EC50 = 683 mg/L), Botrytis cinerea (EC50 = 774 mg/L), Botryodiplodia theobromae (EC50 = 501 mg/L), Fusarium oxysporum (EC50 = 500 mg/L), F. solani (EC50 = 260 mg/L), Penicillium digitatum (EC50 = 417 mg/L), Phytophthora infestans (EC50 = 298 mg/L), and Sclerotinia sclerotiorum (EC50 = 763 mg/L). These compounds based on a biodegradable and biocompatible chitosan could be used as potentially antimicrobial agents in crop protection instead of hazardous synthetic pesticides.
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Huang, Huey-Chun, Hsiao-Fen Wang, Kuang-Hway Yih, Long-Zen Chang, and Tsong-Min Chang. "The Dual Antimelanogenic and Antioxidant Activities of the Essential Oil Extracted from the Leaves ofAcorus macrospadiceus(Yamamoto) F. N. Wei et Y. K. Li." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/781280.
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The antimelanogenic and antioxidant activities of the essential oil extracted from the leaves ofAcorus macrospadiceus(Yamamoto) F. N. Wei et Y. K. Li have never been explored. The essential oil effectively inhibited mushroom tyrosinase activity (EC50= 1.57 mg/mL) and B16F10 tyrosinase activity (IC50= 1.01 mg/mL), decreased the melanin content (EC50= 1.04 mg/mL), and depleted the cellular level of the reactive oxygen species (ROS) (EC50= 1.87 mg/mL). The essential oil effectively scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH) (EC50= 0.121 mg/mL) and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) ABTS+radicals (EC50= 0.122 mg/mL). It also exhibited an apparent reducing power (EC50= 0.021 mg/mL) and metal-ion chelating activity (EC50= 0.029 mg/mL). The chemical constituents of the essential oil are ethers (55.73%), ketones (19.57%), monoterpenes (7.82%), alcohols (3.85%), esters (3.77%), sesquiterpenes (3.72%), and aromatic compounds (2.85%). The results confirm thatA. macrospadiceusessential oil is a natural antioxidant and inhibitor of melanogenesis.
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Bondarenko, Lyubov, Anne Kahru, Vera Terekhova, Gulzhian Dzhardimalieva, Pavel Uchanov, and Kamila Kydralieva. "Effects of Humic Acids on the Ecotoxicity of Fe3O4 Nanoparticles and Fe-Ions: Impact of Oxidation and Aging." Nanomaterials 10, no. 10 (2020): 2011. http://dx.doi.org/10.3390/nano10102011.
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The magnetite nanoparticles (MNPs) are increasingly produced and studied for various environmental applications, yet the information on their ecotoxicity is scarce. We evaluated the ecotoxicity of MNPs (~7 nm) before and after the addition of humic acids (HAs). White mustard Sinapis alba and unicellular ciliates Paramecium caudatum were used as test species. The MNPs were modified by HAs and oxidized/aged under mild and harsh conditions. Bare MNPs proved not toxic to plants (96 h EC50 > 3300 mg/L) but the addition of HAs and mild oxidation increased their inhibitory effect, especially after harsh oxidation (96 h EC50 = 330 mg/L). Nevertheless, all these formulations could be ranked as ‘not harmful’ to S. alba (i.e., 96 h EC50 > 100 mg/L). The same tendency was observed for ciliates, but the respective EC50 values ranged from ‘harmful’ (24 h EC50 = 10–100 mg/L) to ‘very toxic’ (24 h EC50 < 1 mg/L). The ecotoxicity of Fe-ions with and without the addition of HAs was evaluated in parallel: Fe (II) and Fe (III) ions were toxic to S. alba (96 h EC50 = 35 and 60 mg/L, respectively) and even more toxic to ciliates (24 h EC50 = 1 and 3 mg/L, respectively). Addition of the HAs to Fe-ions yielded the respective complexes not harmful to plants (96h EC50 > 100 mg/L) but toxic to ciliates (24 h EC50 = 10–100 mg/L). These findings will be helpful for the understanding of the environmental fate and toxicity of iron-based NPs.
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Yourman, L. F., and S. N. Jeffers. "Resistance to Benzimidazole and Dicarboximide Fungicides in Greenhouse Isolates of Botrytis cinerea." Plant Disease 83, no. 6 (1999): 569–75. http://dx.doi.org/10.1094/pdis.1999.83.6.569.
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In 1996 and 1997, 325 isolates of Botrytis cinerea were collected from 35 commercial greenhouses growing ornamental crops in South Carolina to determine the incidence of resistance to benzimidazole and dicarboximide fungicides. Conidium germination was assessed on a defined agar medium amended with either thiophanate-methyl (a benzimidazole) or vinclozolin (a di-carboximide). A total of 53 representative isolates were evaluated further for conidium germination and mycelium growth on fungicide-amended medium and for infection of geranium seedlings treated with thiophanate-methyl or vinclozolin at label rates. Isolates were considered sensitive to thiophanate-methyl or vinclozolin when the effective concentration of the fungicide active ingredient resulting in 50% inhibition of germination (EC50-germ) was ≤5 μg/ml or when the effective concentration of fungicide active ingredient resulting in 50% inhibition of mycelium growth (EC50-growth) was ≤1 μg/ml. Of all isolates, 81% (262/325) were resistant to thiophanate-methyl and 69% (223/325) were resistant to vinclozolin. Four phenotypes were observed: sensitive to both fungicides (17%), resistant to both fungicides (67%), resistant only to thiophanate-methyl (14%), and resistant only to vinclozolin (2%). Isolates resistant to at least one fungicide were found in 33 of the 35 locations from which samples were taken. Disease incidences on geranium seedlings treated with 600 μg/ml of thiophanate-methyl and then inoculated with isolates sensitive and resistant to this fungicide were 1.4 and 96.1%, respectively. Disease incidences on geranium seedlings treated with 600 μg/ml of vinclozolin and then inoculated with isolates sensitive and resistant to this fungicide were 0.3 and 91.9%, respectively. With thiophanate-methyl, correlation coefficients (r) between disease incidence and log EC50-germ or log EC50-growth were 0.987 and 0.992, respectively. With vinclozolin, correlation coefficients between disease incidence and log EC50-germ and log EC50-growth were 0.975 and 0.893, respectively. Correlation coefficients between the two EC50 values for thiophanate-methyl were 0.989 and for vinclozolin were 0.900. Isolates sensitive to thiophanate-methyl had a mean EC50-germ value of 0.93 μg/ml and a EC50-growth value of 0.11 μg/ml. For isolates sensitive to vinclozolin the mean EC50-germ value was 1.63 μg/ml and the mean EC50-growth value was 0.26 μg/ml. Thiophanate-methyl-resistant isolates had mean EC50-germ and EC50-growth values greater than 500 μg/ml while vinclozolin-resistant isolates had a mean EC50-germ value greater than 500 μg/ml and a mean EC50-growth value of 3.18 μg/ml.
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Zhang, Tao, Zhongxia Zhou, Fabao Zhao, et al. "Identification of Novel Diarylpyrimidines as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors by Exploring the Primer Grip Region." Pharmaceuticals 15, no. 11 (2022): 1438. http://dx.doi.org/10.3390/ph15111438.
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HIV-1 reverse transcriptase (RT) plays a crucial role in the viral replication cycle, and RT inhibitors can represent a promising pathway in treating AIDS. To explore the primer grip region of HIV-1 RT, using -CH2O- as a linker, substituted benzene or pyridine rings were introduced into the left wing of diarylpyrimidines (DAPYs). A total of 17 compounds with new structures were synthesized. It showed that all compounds exhibited anti-HIV-1 (wild-type) activity values ranging from 7.6–199.0 nM. Among them, TF2 (EC50 = 7.6 nM) showed the most potent activity, which was better than that of NVP (EC50 = 122.6 nM). Notably, compared with RPV (CC50 = 3.98 μM), TF2 (CC50 > 279,329.6 nM) showed low cytotoxicity. For HIV-1 mutant strains K103N and E138K, most compounds showed effective activities. Especially for K103N, TF2 (EC50 = 28.1 nM), TF12 (EC50 = 34.7 nM) and TF13 (EC50 = 28.0 nM) exhibited outstanding activity, being superior to that of NVP (EC50 = 7495.1 nM) and EFV (EC50 = 95.1 nM). Additionally, TF2 also showed the most potent activity against E138K (EC50 = 44.0 nM) and Y181C mutant strains (EC50 = 139.3 nM). In addition, all the compounds showed strong enzyme inhibition (IC50 = 0.036–0.483 μM), which demonstrated that their target was HIV-1 RT. Moreover, molecular dynamics simulation studies were implemented to predict the binding mode of TF2 in the binding pocket of wild-type and K103N HIV-1 RT.