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Specific Host Restance: The Effector Mechanisms
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Microbial toxins are of two types, exotoxins and endotoxins. As their names suggest, exotoxins are secreted by the microbe, and endotoxins are not secreted but, instead, are released when the microbe dies. They differ in chemical nature, as well, and the host deals with them in distinct ways. Exotoxins are proteins secreted by only a few of the many bacterial pathogens, but they may be extremely potent virulence factors for the microbes that secrete them. Some exotoxins produce disease when they are ingested with food or water, in such cases there may be no microbial infection or growth in the poisoned individual. Botulism and staphylococcal food poisoning are examples of such exotoxin poisoning. Production of food poisoning in the absence of infection is clearly of no use to the microbe. It is possible that such toxins perform functions important to the microbe which are still unknown and it is only chance that makes them toxic.
Methods and Equipment for Quality Control of Radiopharmaceuticals
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Rolf Zijlma, Danique Giesen, Yvette Kruiter, Philip H. Elsinga, Gert Luurtsema
When a product is not produced under sterile conditions, it could happen that the end solution contains endotoxins. The Endosafe testing module from Charles River is designed for bacterial endotoxin test (Figure 6.4). Endotoxins can be described as a toxic substance released from the membrane of gram-negative bacteria also known as lipopolysaccharide (LPS). The Limulus amebocyte lysta (LAL) test reflects the endotoxin substance from the membrane of gram-negative bacteria. The specification for release criteria of radiopharmaceuticals is <2.50 Endotoxin Units (EU)/ml.
Anti-Cancer Agents from Natural Sources
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Felipe Gonzalez
Bacteria-originated toxins are toxic substances that bacteria secrete to attack other bacteria or host cells. These toxins are classified into two simple forms: endotoxins and exotoxins. Endotoxins are toxic substances that bacteria secrete outside their cell wall. Endotoxins are toxic substances, usually lipids, that are located within the cell (Bacterial Toxins, 2018). Regardless of the mechanism used, damage to the host is negligible viz. toxins are often considered non-invasive and they cause either very limited damage or no damage on their host. A primary advantage of bacterial toxins is that they can attack the host from a distance, requiring them to recognize receptors to bind too. Most toxins produced by bacteria come as proteins that are encoded with the bacterial genes (Wan et al., 2006). Based on bacterial strain and the characteristics of the toxins, they may cause fever, hypotension, shock, hypoglycemia, and ultimately death. Some toxins have been investigated to validate their anticancer activity (Henkel et al., 2010). The few most studied toxins include diphtheria, cytolethal distending, and exotoxin a toxins.
Scorpion envenomation: a deadly illness requiring an effective therapy
Published in Toxin Reviews, 2021
Faez Amokrane Nait Mohamed, Fatima Laraba-Djebari
Pyrogenous reactions elicited by antivenoms are mainly caused by endotoxin contamination. Bacterial endotoxins are outer cell membranes of gram-negative bacteria lipopolysaccharides (LPS) (Erridge and Greer 2002, Elhag and Mahmoud 2017). The molecular mechanism of toxicity is related to Toll-like receptor 4 (TLR4) and/or LPS-binding protein (LPB) receptors interaction located mainly on phagocytes producing pro-inflammatory cytokines TNF-α, IL-6, IL-1β and other cytokines (Morais and Massaldi 2009). According to Gutiérrez et al. (2017), the preclinical assessment of antivenoms regarding the concept of the 3Rs (reduction, replacement, and refinement) is necessary to avoid adverse reactions in patients, especially contamination by microorganisms (Gutiérrez et al.2017).
Safety and tolerability of fixed-dose combinations of ibuprofen and acetaminophen: pooled analysis of phase 1–3 clinical trials
Published in Postgraduate Medicine, 2021
Jiangfeng Su, Rina Leyva, David Kellstein, Mario Cruz-Rivera, Suzanne Meeves
The FDC IBU/APAP 250 mg/500 mg dose, which was chosen for commercial development, was generally well tolerated in this analysis; the most commonly reported all-causality TEAEs occurring with this dose were nausea, vomiting, and dizziness. It should be noted that 3 of the 7 trials in this pooled analysis, comprising 73.5% of the overall population, were in the third molar extraction model of dental pain. While some TEAEs may be causally related to use of the trial drug, these specific AEs are commonly encountered in those undergoing extraction of wisdom teeth and may be related to the pain and trauma of surgery and/or the use of opioid rescue medication [26]. Indeed, the incidence of nausea and vomiting was higher in the placebo group, which had greater use of opioid rescue medication than the active treatment groups. In the induced-fever trial, administration of the endotoxin elicited an acute illness, symptoms of which included nausea. In this analysis the incidence of these and most other TEAEs was consistently greater in the placebo arm (mainly due to lack of symptom control by placebo) than in the FDC arms, and the incidence of treatment-related AEs was quite low.
Interaction of nanoparticles with endotoxin Importance in nanosafety testing and exploitation for endotoxin binding
Published in Nanotoxicology, 2021
Maria Mangini, Alessandro Verde, Diana Boraschi, Victor F. Puntes, Paola Italiani, Anna Chiara De Luca
Endotoxin persists in the environment also in the absence of living Gram-negative bacteria. In the lab, it can be found in all chemicals and glassware, and its high thermostability makes it resistant to the majority of the sterilization methods usually applied (e.g. standard autoclaving). LPS can bind to cationic surfaces, thanks to its negative charge, and to hydrophobic materials through its lipidic domain. While other inflammation-inducing microbial agents can be easily removed with sterilization procedures, the thermostability and the capacity to bind to both hydrophilic and hydrophobic materials, together with its high potency towards human cells, make LPS the most important pyrogen to which attention should be paid during the synthesis and the manipulation of pharmaceutic preparations. LPS can easily bind cationic NPs through electrostatic interactions, such as Coulomb and van der Waals forces (Darkow et al. 1999), and to NPs with a lipophilic surface by hydrophobic interaction with lipid A (Bromberg et al. 2010). LPS contamination of NPs is further facilitated by the high NP surface:volume ratio that increases their reactivity (Jones and Grainger 2009).