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Inhalation Toxicity of Metal Particles and Vapors
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
Certain functional peculiarities make the lung vulnerable to toxic injury. Although situated deep within the body, the lung is in immediate contact with the external environment during each breath. During strenuous exercise or labor, the frequency and depth of respiratory effort, and as a result air intake, is markedly increased, leading to potentially greater toxic exposure. Secondly, the alveolar lining cells have a large surface area and thin cytoplasm with few organelles. This combination of large absorbing surface and modest defensive ability renders Type I cells vulnerable to toxic injury. Thirdly, the alveolar surface is extremely large, an area of approximately 140 m2 in the adult human (Weibel, 1984) (as compared with a skin area of about 2 m2), and its abundant thinwalled capillaries lie in intimate contact with epithelium. The alveolar surface represents the largest area in the body at which the blood comes into virtually direct contact with the external environment. Consequently, toxic particles and vapors are capable not only of injuring extensive areas of alveolar tissue and adjacent structures but also of initiating rapid absorption and distribution throughout the body to injure specific (target) organs, or the body as a whole.
Pathophysiologic Mechanisms of Acute Renal Failure
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Acute renal failure is one of the most common problems in nephrology. It occurs in a wide variety of clinical settings because acute renal failure can result from hypotension and shock, septicemia, rhabdomyolysis, and nephrotoxic drugs, such as aminoglycoside antibiotics, amphotericin B, radiographic contrast agents, acetaminophen, and cisplatin. Common to all forms of acute renal failure is cellular injury involving primarily the renal tubular epithelial cells in the S2 and S3 segments of the proximal tubule, but also involving epithelial cells in the thick ascending limb of the loop of Henle, as well as possibly involving glomerular epithelial and endothelial cells and renal vascular cells.1–3 Depending on whether one is studying ischemic or toxic injury and experimental or human disease, the specific sites and distribution of injury may vary somewhat. Nevertheless, there are some commonalities among all forms of acute renal failure in terms of nephronal patterns of injury as well as cellular mechanisms of injury. In any particular instance of acute renal failure, the factors to be discussed below will participate in varying degrees.
Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Obstruction of the normal bile outflow from hepatocytes causes either abnormal retention of bile within the liver cell or the accumulation of abnormal amounts of biliary substances in the blood.40,312,611 These are representative of the mechanisms of intrahepatic or extrahepatic cholestasis. Increased retention of bile in bile passages produces stagnation and mechanical dilatations of bile canaliculi and ductules. This stasis influences intrahepatic blood circulation and metabolism. Increased amounts of biliary substances in the blood may cause toxic injury to the hepatic cells.445,447 Extrahepatic biliary obstruction produces different degrees of injury.
State-of-the-art of ultrasound-triggered drug delivery from ultrasound-responsive drug carriers
Published in Expert Opinion on Drug Delivery, 2022
Ching-Hsiang Fan, Yi-Ju Ho, Chia-Wei Lin, Nan Wu, Pei-Hua Chiang, Chih-Kuang Yeh
The development of new tools to locally and non-invasively delivering therapeutic substances at the tumor tissue without affecting elsewhere in the body has been a long sought-after goal in the tumor treatment field. Among the established methods, US could be used to supply mechanical pressure waves to delivery of a variety of therapeutic substances from US-responsive particles with spatial precision of several millimeters in deep-seated tissues. However, the biosafety and pharmacokinetics of US-triggered drug delivery were still required to investigate to prevent thermal, mechanical, and toxic injury after treatment. As the various advantages of US systems – convenience, exogenous administration, noninvasiveness, deep focus, and theranostic capabilities – suggest their potential for extensive medical applications in tumor therapy, thrombolysis, tissue engineering, wound healing, and vaccination.
Identification of odor biomarkers in irradiation injury urine based on headspace SPME-GC-MS
Published in International Journal of Radiation Biology, 2021
Xin Wu, Tong Zhu, Hongbing Zhang, Lu Lu, Xin He, Changxiao Liu, Sai-jun Fan
Biomarkers are biochemical indicators that mark changes in the structure or function of systems, organs, tissues, cells and subcellular components, which can reflect biological processes closely related to physiological or pathological conditions. When the organism is seriously damaged, as a signal indicator, its biochemical metabolism process is disordered, resulting in changes in metabolite content or abnormal metabolites. Recently, with the rapid development of metabolomics, the discovery of small molecule biomarkers has received extensive attention and a breakthrough has been made, especially the application of non-targeted and targeted metabolomics in radiation biodosimetry (Becker et al. 2012; Wu and Qu 2015; Pannkuk et al. 2017; Chen et al. 2018). Biomarkers can be used not only to diagnose severe toxic injury, but also to evaluate the effectiveness of specific medical countermeasures.
Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory mice
Published in Drug and Chemical Toxicology, 2020
Waleed A. Q. Hailan, Faisal M. Abou-Tarboush, Khalid M. Al-Anazi, Areeba Ahmad, Ahmed Qasem, Mohammad Abul Farah
This may explain the findings arrived at in this part of the research showing that there was a statistically significant increase in the mean level of ALP in the third treated group due to the growth of liver. Our ALP data is in accordance with the previous reports on gemcitabine (Coeman et al. 2000). Moreover, significant elevations in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also recorded in the first treatment category of animals, although there were no statistically significant differences in the means of this enzyme in the second and third treated groups compared with the control group, due to the internal recovery process of the body. Injury to the liver resulting in the necrosis of hepatocytes leads to the elevated release of these AST and ALT in the blood stream, thus their levels in the sera increases upon any toxic injury to the liver (Nyblom et al. 2006). In general, the alterations in the levels of aminotransferases offer a strong indication of toxicity that includes necrosis or cellular degeneration in the liver and/or kidney (Hassoun and Stohs 1995). This can explain the elevation in the levels of these enzymes a week after the treatment, which coincided with histological changes like necrosis in the liver specimens taken from the animals of this group. Our results corroborate the previous reports available on gemcitabine studies (Robinson et al. 2003, Okada et al. 2011, Hryciuk et al.2018, Mihăilă 2017).