Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
The last murine models presented here concerns acute lethal infection and bacteremia. In the first, microbial cultures are adequately diluted with bacteriological mucin and neutropenia is also induced by administration of cyclophosphamide. The infection is induced by intraperitoneal injection, which results in 100% mortality in untreated controls within 48 to 72 hours after infection. The antimicrobial agent should be administered between 10 and 15 minutes after infection, intravenously or subcutaneously. Mortality must be recorded daily. Animals that survive after seven days of treatment must be euthanized. The effective dose in reducing mortality by 50% (DE50) is calculated (Jabés et al. 2011). In the murine model of bacteremia, the bacterial suspension is also injected intraperitoneally into the animal. The antimicrobial agent is injected immediately after infection. After two hours, blood samples are collected, which are sown in plates containing culture medium, which will be incubated for later counting the number of CFUs. Animal mortality is also observed for up to seven days (Liu et al. 2017b).
MRCPsych Paper A1 Mock Examination 1: Answers
Melvyn WB Zhang, Cyrus SH Ho, Roger Ho, Ian H Treasaden, Basant K Puri in Get Through, 2016
Explanation: Therapeutic index is the relative measure of the toxicity or safety of a drug and is usually defined as the ratio of the median toxic dose to the median effective dose. The median toxic dose is defined as the dose at which 50% of the patients would experience specific toxic effects. The median effective dose is defined as the dose at which 50% of the patients would have a specified therapeutic effect. A drug with a high therapeutic index implies that a wide range of dosages of the drug could be prescribed. Conversely, if the therapeutic index is low, closer monitoring of the prescribed medication would be essential.
Quantifying cell kill and cell survival
Michael C. Joiner, Albert J. van der Kogel in Basic Clinical Radiobiology, 2018
A cell survival curve is a plot of surviving fraction S against dose D (of radiation, cytotoxic drug or other cell-killing agent). Figure 4.3a shows that when plotted on linear scales, the survival curve for cells irradiated in tissue culture is often reverse-sigmoid: there is a shoulder followed by a curve that asymptotically approaches zero survival. To indicate the sensitivity of the cells to radiation, we could just read off the dose that kills say 50% of the cells. This is sometimes called the ED50 (i.e. effect dose 50%). Sometimes ED90 is used. In doing this we need make no assumptions about the shape of the curve.
Synergistic effect of ursolic acid and piperine in CCl4 induced hepatotoxicity
Published in Annals of Medicine, 2021
Sayan Biswas, Amit Kar, Nanaocha Sharma, Pallab K. Haldar, Pulok K. Mukherjee
Isobologram method and the median effect method proposed by Chou and Talalay were used to analyze the interaction between combinations of UA and PIP [31]. In this method, the different dose combinations of UA + PIP were plotted against their respective effects (ED50, ED75 and ED90) in the form of percent hepatoprotective effect as mentioned in Equation 1. Here ED50 stands for median effective dose whereby the desired therapeutic effect produced is 50% [32]. Similarly, ED75 and ED90 stand for the therapeutic effect of 75% and 90% respectively. The doses are then connected through the line of additivity. A combination was taken as synergistic, antagonistic or additive when the observed dose combination falls below, above or on the line of additivity respectively. An extended combinational effect (synergism, antagonism, additivity) for UA and PIP was also determined by median effect analysis of Chou Talalay using COMPUSYN software 2.0 to obtain a combination index, a quantitative measure of synergism. The combination index (CI) values of less than 0.3 indicate strong synergism, the value of 0.3–0.69 indicates synergism, 0.70–0.84 indicates moderate synergism, 0.85–0.89 indicates mild synergism, 0.9–1.09 indicates additive effect, 1.10–1.19 indicates slight antagonism, 1.20–1.44 indicates antagonism, >1.45 indicates moderate strong antagonism [33].
The first World Health Organization International Standard for infliximab products: A step towards maintaining harmonized biological activity
Published in mAbs, 2019
Clive Metcalfe, Thomas Dougall, Chris Bird, Peter Rigsby, Marie-Emmanuelle Behr-Gross, Meenu Wadhwa, participants of the study
After establishing that candidate 16/170 was fit for purpose to serve as the IS for infliximab, we conducted an in-house study to gauge its suitability to determine relative TNF neutralization potencies of different infliximab products. Remicade® (2 batches), Remsima® (2 batches) and Flixabi® (1 batch) were assayed for TNF neutralisation in duplicate L929 cell cytotoxicity assays. ED50 values were determined for the samples and expressed as a percentage potency of the ED50 of candidate IS 16/170; data from a representative assay is shown in Figure 4. Relative to the candidate IS, the two batches of Remicade® showed mean potencies of 102.4% and 105.7% (n = 2), the two batches of Remsima showed mean potencies of 112.7% and 106.4% (n = 2) and the batch of Flixabi® showed a relative potency of 94.5% (n = 2). This confirmed that the candidate IS 16/170 was suitable for use in calibrating assays involving both originator infliximab and biosimilar products.
Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside
Published in OncoImmunology, 2018
S. Faraj, M. Bahri, S. Fougeray, A. El Roz, J. Fleurence, J. Véziers, M. D. Leclair, E. Thébaud, F. Paris, S. Birklé
Cell viability was measured using the MTT assay,51 using the Cell Proliferation Kit I (Roche Diagnostic, # 11465 007 001) according to the manufacturer's instructions. Tumor cells (IMR5: 1 × 104 cells; LAN1: 5 × 103 cells; LAN5: 1 × 104 cells; NXS2: 5 × 103 cells) were seeded into 96-well plates in 100 µl of media. The next day, 50 µl (3 times concentrated) of several topotecan and/or mAb 8B6 concentrations prepared in 1:2 serial dilutions were added. After 72 hours, 10 µL of methylthiazole tetrazolium salt stock solution (provided with the kit) were added and incubated at 37°C for 4 hours. Then, 100 µl of solubilization buffer (provided with the kit) were added and the plates incubated for 4 hours at 37°C for color development. Absorbance was recorded at 570 nm against a reference wavelength at 650 nm on a Multiskan reader (Thermo Electron, Walthman, MA, USA). Assays were performed in quadruplicate and experiments were repeated three times. Percentage survival for each dose was calculated by multiplying absorbance values with 100 and divided by control absorbance value. Dose-response curves were analyzed using CompuSyn software (ComboSyn, Inc, Paranus, NJ, USA) to determine the effective dose 50 (ED50) values.
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- In Vitro
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