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Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Published in Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White, Advances in Spinal Fusion, 2003
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White
Macrophages incorporate LDL via the scavenger receptors. Point mutation in IRS-1 blocks the action of glucose transporter, GLUT4, while PPAR 7 simultaneously promotes differentiation/induction of fat cells, resulting in bulky fat cells. Large fat cells secrete various cytokines, feedback signals, and inhibit phosphorylation of insulin receptors and expression of GLUT4, which transforms macrophages to foam cells, increasing fat cells (Fig. 21). The foam cells cannot phagocytose abnormally ossified cartilage tissues, and the disorder progresses.
Nanomedicines for the Treatment of Cardiovascular Disorders
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Shivani Verma, Puneet Utreja, Mahfoozur Rahman, Lalit Kumar
Atherosclerosis is one of the most common cardiovascular disorder which originates from improper lipid metabolism leading to inflammation of the arterial wall. The maladaptive inflammatory response is also considered as a cause of generation of atherosclerosis (Schiener et al., 2014). Atherosclerosis complications are associated with levels of low-density lipoprotein (LDL) which has a great influence on various cardiovascular events. LDL promotes arterial leukocyte infiltration by the enhancement of endothelial cell adhesion expression (Weber and Noels, 2011). Atherosclerosis stages are recognized through the leukocyte accumulation in the arterial wall. Inflammatory cell adhesion on the arterial wall occurs through various adhesion molecules like vascular cell adhesion molecule (VCAM1), intercellular adhesion molecule (ICAM1), and P-selectin (Zernecke and Weber, 2005). Furthermore, neutrophils and monocytes accumulation on arterial wall involves the integral role of receptors like CC-chemokine receptor 1 and CXC-chemokine receptor 2 (Zernecke et al., 2008). At the end stage of atherosclerosis, excessive proliferation of plaque resident macrophages occurs which promote leukocyte accumulation in higher content on the wall of arteries leading to the formation of atherosclerotic lesions (Andrés et al., 2012). Furthermore, macrophages present in lesions engulf the modified lipoproteins through the activation of scavenger receptors, producing a new cellular structure called foam cells (de Vries and Quax, 2016). Figure 8.6 describes the various phases of development of atherosclerosis (Psarros et al., 2012). Being a multifactorial disease different approaches have been implemented for its treatment and prevention. Therefore, nanomedicines based strategies have been explored to target specific cells or tissues to treat atherosclerosis (Antoniades et al., 2010). Various targeting strategies for atherosclerosis treatment using nanomedicines is explained in Figure 8.7 (Lobatto et al., 2011).
Weakly acidic carboxy group-grafted β-cyclodextrin-threaded acid-degradable polyrotaxanes for modulating protein interaction and cellular internalization
Published in Science and Technology of Advanced Materials, 2021
Shunyao Zhang, Atsushi Tamura, Nobuhiko Yui
In our previous studies, acid-degradable β-CD PRXs were chemically modified with hydrophilic oligo(ethylene glycol) chains (e.g. 2-(2-hydroxyethoxy)ethyl carbamate; HEE) for increasing the solubility in aqueous media [7,17]. Although the chemical modifications of PRXs are essential for improving their solubility in aqueous media, the highly hydrophilic functional groups generally disturb cellular internalization and tissue accumulation. To further improve the therapeutic efficacy of β-CD PRXs, the molecular design of PRXs should be optimized. One potential method for improving the cellular internalization efficiency of PRXs is modification with targeting biomolecules, such as peptides, saccharides, antibodies, and aptamers [27–31]. These targeting molecules interact with specific receptors, enabling selective and highly efficient targeting to specific cells. However, chemical modification of these targeting biomolecules generally requires delicate reaction conditions, and it is difficult to achieve scalable synthesis. Another potential approach for improving the cellular internalization efficiency of PRXs is optimization of the physicochemical characters of PRXs, such as hydrophilicity–hydrophobicity, charge, molecular weight, and threading ratio of CDs. Among these, the chemical modification of charged functional groups potentially improves cellular internalization efficiency [32,33], because both cationic and anionic functional groups facilitate the interaction of PRXs with proteins through electrostatic interactions. We previously reported that weakly acidic carboxymethyl ether-modified α-CD PRX showed selective and high intracellular uptake in a macrophage-like cell line (RAW 264.7 cells), whereas it exhibited negligible uptake in fibroblasts (NIH/3T3 cells) [34]. We considered that the carboxy groups increased the interaction with macrophage scavenger receptor A (MSR-A), which recognizes anionic macromolecules [35], resulting in selective and high intracellular uptake in macrophage-like cell lines. Because macrophages plays a central role in the progression of atherosclerosis and inflammatory diseases [36,37], carboxylation of acid-degradable β-CD PRXs is promising for therapeutic applications in cholesterol-related metabolic diseases such as atherosclerosis.
Influence of quartz exposure on lung cancer types in cases of lymph node–only silicosis and lung silicosis in German uranium miners
Published in Archives of Environmental & Occupational Health, 2018
Stefan Mielke, Dirk Taeger, Kerstin Weitmann, Thomas Brüning, Wolfgang Hoffmann
Four main biological pathways are discussed as the molecular pathology of silicosis. First, crystalline quartz dust contact causes an inflammation reaction in lung parenchyma communicated by alveolar macrophages.49,50 Second, quartz dust directly increases the concentration of reactive oxygen species (ROS)51 or nitrogen species in mice.52 Third, while the role of direct cytotoxicity is still unclear, inflammation and ROS are not only able to manipulate gene expression and gene integrity53 but also signal transduction.54 Fourth, silica contact can cause a higher lysosomal permeability through the insufficient process of internalization with consecutive cell death and proinflammatory cytokine release.52 The scavenger receptor macrophage receptor with collagenous structure (MARCO) expressed on alveolar macrophages may play an important role in internalization of silica particles.55 Building a NALP3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome,10,56 releasing proinflammatory cytokines such as interleukin 1 beta (IL-1β)10,57 or tumor necrosis factor alpha (TNF-α),10,56,58,59 and stimulating transcription factor NF-κB (nuclear factor–kappa-light-chain-enhancer of activated B-cells)60,61 can be the leading ways of chronic inflammation. In the mice model, a disturbed balance between the more suppressive alveolar macrophages and the more stimulatory dendritic cells with a higher lung parenchyma emigration of dendritic cells is the consequence.62 In the absence of lymphocytes, silica-induced inflammation can prosper through NALP3 inflammasome modulation as a lymphopenic mice model has shown.63 Moreover, cyclooxygenase activity and prostaglandin synthesis are affected by silica particles.64 Furthermore, it was shown that cytokines TGF-β1 (transforming growth factor beta 1) can induce epithelial to mesenchymal transition,65 maybe also as a first step of cell degeneration as an inflammation consequence. Immunology in silicosis is a complex mixture of more pro- but also anti-inflammatory interactions.66 There is some evidence that quartz dust causes chronic inflammation as the main pathogenic process,51,67,68 especially since silica-induced apoptosis stimulates inflammation by releasing former ingested silica particles.66,69