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Parasite Versus Host: Pathology and Disease
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
In Figure 5.1A, parasites with different thresholds of disease are illustrated. Two factors that may influence virulence, and therefore whether the threshold is relatively high or low, are the mode of transmission utilized by the parasite as well as its ID-50 (the average number of infectious parasites to which hosts must be exposed, to infect 50% of those hosts). In general, as the ease of transmission goes up or as the ID-50 goes down, the threshold decreases. Explain these observations.
Measuring Infectivity
Published in Johan Giesecke, Modern Infectious Disease Epidemiology, 2017
The AR clearly increases with dose, and it seems that a dose of around 1,000,000 bacteria will cause disease in half the subjects exposed. This figure is sometimes called ID50 (= the dose of a pathogen that will cause disease in 50% of exposed susceptibles). A possible error in calculations such as these is that some of the ill subjects were not infected in the experiment, but that they became secondary cases to some real primary case. The authors assure the reader, however, that this could not have happened. One should also note that the number involved in the study was small and therefore the confidence intervals for the ARs will be very wide (for the estimate 33% in the middle line in the table the 95% confidence interval will be from –5% to 71%, using the formula for a proportion in Chapter 7).
Standardized Allergen Vaccines in the United States
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2014
Ronald L. Rabin, Jay E. Slater
In the ID50EAL method, allergenic vaccines are evaluated in subjects maximally reactive to the respective reference concentrates. Each subject is tested with serial threefold dilutions of the reference extract. After 15 min, the sum of the longest and midpoint orthogonal diameters of erythema (ΣE) is determined at each dilution, and the log dose producing a 50 mm ΣE response (D50) is calculated [13]. Vaccines that produce similar D50 responses are considered bioequivalent and are assigned similar units, the bioequivalent allergy unit (BAU). Because the modal D50 of a series of vaccines was 14 (a 3-14 or 1:4.8 million dilution), vaccines with a mean D50 of 14 were arbitrarily assigned the value of 100,000 BAU/ml [11]. Thus, the formula for the determination of potency from the D50 is:
Synthesis and biological activity evaluation of 3-(hetero) arylideneindolin-2-ones as potential c-Src inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Salvatore Princiotto, Loana Musso, Fabrizio Manetti, Valentina Marcellini, Giovanni Maga, Emmanuele Crespan, Cecilia Perini, Nadia Zaffaroni, Giovanni Luca Beretta, Sabrina Dallavalle
N-Terminal His6-tagged Src was purchased from Merck-Millipore (cat. 14–326). The reaction was performed according to the manufacturer’s instructions with minor modifications: 500 μM Src-peptide (KVEKIGEGTYGVVYK), 100 μM ATP, 0.00087% NP-40, 10 ng of the enzyme, 10% DMSO in 10 μL at 30 °C for 10 min. To avoid peptide adsorption to the plastic surface, protein low-binding tubes were used. ADP-Glo Kinase Assay (Promega) was then used to detect kinase activity accordingly with manufacturer’s instruction with minor modifications. In details, reactions were transferred to white 384 well-plates and stopped by adding 10 µL of ADP-Glo Reagent (Promega) for 50 min at rt. 20 μL of Detection Reagent (Promega) was then added for 30 min and the reaction read using GloMax Discover microplate reader (Promega). Data were plotted using GraphPad Prism 5.0. ID50 values were obtained according to Equation (1)50 is the 50% inhibitory dose. Compounds tested were assumed to act as fully ATP-competitive inhibitors. Therefore, Ki values were calculated accordingly to Equation (2). Ki is the affinity of the inhibitor to the enzyme, [S] is the substrate (namely, ATP) concentration, and Km is the affinity of ATP calculated accordingly to Michaelis-Menten equation.
Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies
Published in Expert Review of Vaccines, 2021
Lianlian Bian, Fan Gao, Jialu Zhang, Qian He, Qunying Mao, Miao Xu, Zhenglun Liang
Shen et al. employed a lentivirus-based pseudovirus assay to show neutralization against the variant B.1.1.7 in 40 recipients of the Moderna vaccine and found that the B.1.1.7 variant was neutralized by the vaccine sera, although with modestly diminished susceptibility compared to the D614G variant. The median ID50 and ID80 titers of immune sera were, on average, 2.1-fold and 1.7-fold lower, respectively, against B.1.1.7 than that against D614G [36]. Wu et al. used two orthogonal vesicular stomatitis virus (VSV) and lentivirus pseudovirus neutralization (PsVN) assays that expressed spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants to assess the neutralizing capacity of sera from humans immune to the Moderna vaccine. No significant impact was found on the neutralization of Moderna vaccine-immune sera against the B.1.1.7 variant, whereas reduced neutralization was measured against the mutations present in B.1.351. VSV pseudoviruses with spikes containing K417N-E484K-N501Y-D614G and full B.1.351 mutations showed a 2.7 – and 6.4-fold reduction in GMT, respectively, compared to the D614G VSV pseudovirus [62].
Evaluating revefenacin as a therapeutic option for chronic obstructive pulmonary disease
Published in Expert Opinion on Pharmacotherapy, 2020
Sabina Antonela Antoniu, Ruxandra Rajnoveanu, Ruxandra Ulmeanu, Florin Mihaltan, Mihaela Grigore
In vivo testing comparatively evaluated the pharmacological properties (bronchodilating potency, duration of action, and M3 selectivity) of TD-4208, glycopyrronium, and tiotropium in rats and dogs separately for single or repeated (seven) doses. Bronchodilating potency and onset of action at various single doses (3, 10, and 30 mg/kg) of inhaled TD-4208 were tested in dogs. A dose-dependent bronchodilating effect, which was significantly superior to that of placebo (inhaled vehicle), was observed. The onset of action for all doses was 5 min after dosing. The duration of bronchodilating effect was also found to be dose dependent, with only two higher doses resulting in >24 h sustained inhibitory effects. The other two LAMAs tested were also found to exert significant antimuscarinic effects compared with placebo [8,9]. Similar effects were found with both single and multiple doses on methacholine-induced bronchoconstriction in rats. The dose producing 50% inhibitory effect (ID50) was 45 mg/mL with single dosing and 36 mg/mL for repeated dosing.