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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.
Immune Modulation In Sepsis
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Janet M. J. Hammond, Peter D. Potgieter
Interleukin 10 Interleukin 10 (IL-10) is an 18-kDa cytokine produced by a variety of cells, including T cells, B cells, monocytes, and macrophages [104], This cytokine, originally identified as “cytokine synthesis inhibitory factor,” inhibits the synthesis and gene expression of IL-1, TNF, IL-6, IL-8, and colony stimulating factors [105,106]. It has been detected in the plasma of patients with sepsis and after the administration of lipopolysaccharide to animals [107–110].
Genetic Control of Endotoxin Responsiveness: The Lps Gene Revisited
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Stefanie N. Vogel, Nayantara Bhat, Danielle Malo, Salman T. Qureshi
Recently Kuhns et al. (1) described a young patient with recurrent bacterial infections who was highly refractory to lipopolysaccharide (LPS) both in vivo and in vitro. Based on the failure to produce various cytokines in response to LPS, in the face of normal expression of CD 14 and other cell surface markers and normal responsiveness to other stimuli, the authors concluded that the LPS hyporesponsiveness exhibited by this patient was the result of a mutation very early in the LPS signal transduction pathway. This report represents the first description of a human condition that is phenotypically very similar to that of inbred mouse strains that possess a defective allele at the Lps locus. In addition to their profound refractoriness to LPS, both in vivo and in vitro, mice that bear a mutation within the Lps gene exhibit greatly increased susceptibility to bacterial infections as well (reviewed in Ref. 2). In spite of the fact that a number of knockout mice have been recently demonstrated to exhibit mitigated responses to LPS (3), a mutation within Lps leads to the most profound state of endotoxin hyporesponsiveness described to date.
Maintaining a ‘fit’ immune system: the role of vaccines
Published in Expert Review of Vaccines, 2023
Béatrice Laupèze, T. Mark Doherty
The exact nature of innate immune response that occurs influences the activation of B cell and T cell subsets that determine the type of adaptive response that follows [15]. Different PRRs recognize different PAMPs expressed by different classes of pathogens (viruses or bacteria) and the activation of different combinations of PAMPs leads to different responses by innate immune cells. For example, certain lipopolysaccharides common to bacterial membranes may provoke the activation of innate immune cell processes that promote the kind of inflammatory profile associated with bacterial infection (and sepsis). By contrast, recognition of certain nucleic acids, such as 5′ triphosphate RNA, which is uncommon in mammalian hosts, may promote immune pathways associated with anti-viral responses [13]. These initial innate immune responses are not specific to individual pathogens but neither are they wholly nonspecific.
Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy
Published in Journal of Drug Targeting, 2023
Yulu Zhang, Yu Long, Jinyan Wan, Songyu Liu, Ai Shi, Dan Li, Shuang Yu, Xiaoqiu Li, Jing Wen, Jie Deng, Yin Ma, Nan Li
Bacterial infections are the most common type of infectious disease and can affect a wide range of organs and tissues, even causing sepsis and septic shock, and have serious public health consequences [98,99]. Endotoxin, also known as lipopolysaccharide (LPS), is an important pathogenic trigger for Gram-negative bacterial sepsis. It can reach target organs after circulation and cause lethal damage to the organism [100,101]. Effective removal of LPS is an important method for the successful treatment of bacterial infections and their complications. Macrophages are cells that can respond rapidly to microenvironmental signals. During bacterial infection, macrophages are among the first responders. Macrophages recognise pathogen-associated molecular patterns (PAMPs), such as LPS, through toll-like pattern recognition receptors on them [102]. LPS binding to macrophages activates TLR4 and activates transcription factors (e.g. interferon regulatory factors) and NF-κB to initiate inflammatory responses as a means of regulating bacterial phagocytic uptake and intracellular transport [103]. Therefore, the critical role played by macrophages and their surface receptors in LPS signalling provides new ideas for the treatment of bacterial infections and their complications.
Deer antler based active ingredients have protective effects on LPS/d -GalN-induced acute liver injury in mice through MAPK and NF-κB signalling pathways
Published in Pharmaceutical Biology, 2022
Guixiang He, Quanmin Zhao, Yan Zhao, Ying Zong, Shigang Gu, Mengjie Li, Renjie Li, Jiaxin Sun
Macrophages are the most important immune cells and play a variety of immunomodulatory roles in various inflammatory diseases. Once activated, macrophages release a series of inflammatory cytokines (Fujiwara and Kobayashi 2005). Lipopolysaccharide is a cell wall component of Gram-negative bacteria, which interferes with the receptors of immune cells (Chen et al. 2018). Lipopolysaccharide is one of the most potent activators of mononuclear macrophages and is known to produce pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α and pro-inflammatory mediators, such as NO and PGE2 (Yang et al. 2012; Abarikwu 2014). Therefore, we selected mouse monocyte macrophages RAW 264.7 to screen the isolated and purified antler base protein extract, and found that the NO production of RAW264.7 cells after 4 h pre-treatment with R1 protein component was significantly reduced. We also measured the cytokines IL-6, IL-1β and TNF-α to further verify the anti-inflammatory effect of the R1 protein component. The results demonstrated that pre-treatment with R1 protein component, inflammatory factors were reduced in a dose-dependent manner. Therefore, we speculate that the R1 protein component of deer antler base may have a pre-protective effect on ALI through anti-inflammatory effects.