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The Pathogenetic Role of Anti-Phospholipid Antibodies in Thrombosis
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
R. H. W. M. Derksen, P. Hasselaar, Ph.G. de Groot
Cariou et al.31 described a significant inhibition of the rate of activation of purified protein C by HUVEC in the presence of thrombin with 8/8 LA-positive IgGs or F(ab’) fragments. This effect could be neutralized by incubation with a greater quantity of phospholipids (PC, PS). Patient IgG similarly inhibited protein C activation using purified rabbit thrombomodulin. There was no relation between these abnormalities and a history of thrombosis.
Nanosuspensions as Nanomedicine: Current Status and Future Prospects
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Shobha Ubgade, Vaishali Kilor, Abhay Ittadwar, Alok Ubgade
Considering the poor water solubility of most of the chemical moieties, organic solvents are required in the formulation in most of the cases, especially when emulsion and microemulsion as a template is used. The acceptability of the organic solvents in the production of pharmaceuticals, their toxicity potential and the ease of their removal from the formulation needs to be considered when formulating nanosuspensions. The pharmaceutically acceptable and less hazardous water-miscible solvents, such as isopropanol and ethanol, and partially water-miscible solvents, such as ethyl formate, ethyl acetate, butyl lactate, triacetin, propylene carbonate and benzyl alcohol, are preferred over the conventional hazardous solvents, like dichloromethane.
The Rat
Published in Francis L. S. Tse, James M. Jaffe, Preclinical Drug Disposition, 2017
Francis L. S. Tse, James M. Jaffe
The test compound is usually administered beginning on day 6 postconception (PC) and continuing through day 15 PC, which is an accepted period of dosing to cover organogenesis. Dosing prior to day 6 PC could kill the embryo before it implants.
Cold stored platelets in the management of bleeding: is it about bioenergetics?
Published in Platelets, 2023
Chloe E. George, Christine V. Saunders, Alex Morrison, Tom Scorer, Sarah Jones, Nina C. Dempsey
The manufacture of PC exposes them to stresses, such as centrifugation, manipulation, suspension in chemical storage medium and exposure to foreign surfaces such as the plastic of blood bags [33], as well as the loss of protection that is conferred by the endothelium when in the circulation. All of these stressors can cause physiological responses that resemble platelet activation [29,30], hence many of the assays used to study the PSL are functional assays similar to those used to study platelet activation for diagnostic purposes in patients. PC are currently stored in a medium that enables them to be metabolically active, at 20–24°C with constant agitation, in a pack that enables gaseous exchange. During storage at this temperature, glycolysis is enhanced and mitochondrial function is reduced leading to glucose depletion, increased lactate production and a resulting acidification of the PC [30]. For this reason, assessment of platelets during storage often includes and benefits from measures of metabolism and mitochondrial health.
The clinical toxicity of imidacloprid self-poisoning following the introduction of newer formulations
Published in Clinical Toxicology, 2021
Varan Perananthan, Fahim Mohamed, Seyed Shahmy, Indika Gawarammana, Andrew Dawson, Nicholas Buckley
Worse clinical outcomes in imidacloprid toxicity could be due to the higher dose seen in the latter cohort but also could be due to solvents, stabilisers and surfactants present in newer formulations of imidacloprid [22,23]. Stabilisers and surfactants in imidacloprid products vary between brands but are not generally disclosed. Common solvents in pesticide formulations vary from low toxicity substances (water, glycerol, propylene glycol, propylene carbonate) to more toxic hydrocarbons. Some formulations of imidacloprid contain N-methyl-2-pyrrolidone (NMP) and dimethylsulfoxide. NMP causes developmental toxicity in rat studies including decreased foetal body weight, incomplete ossification of skulls and malformations [24]. NMP may also cause central nervous depression, gastrointestinal irritation and hyperglycemia [15]. Features of gastrointestinal toxicity were common prior to 2007 and post 2010. Non-specific gastrointestinal symptoms can occur in large volumes of glycerol intake. Furthermore, NMP present in most formulations is corrosive and in large volumes can induce a reactive gastropathy causing abdominal pain [15].
Process parameters of microsphere preparation based on propylene carbonate emulsion-precursors
Published in Journal of Microencapsulation, 2021
Various solvents have been extensively described for such systems, but the use of non-toxic solvents is often suggested in order to avoid issues connected with a complete solvent removal from the microparticulate matrix due to the low toxicity potential of these solvents (Allhenn and Lamprecht 2011; Elkharraz et al.2011, Ali and Lamprecht 2013). However, despite being non-toxic, these solvents also involve technical limitations. The main limitation is a high intrinsic viscosity, which makes e.g. the control of droplet sizes during emulsification troublesome and slows down the diffusion of the solvent from the droplets, subsequently risking a failure in microsphere obtainment. In this context, propylene carbonate (PC) exhibits beneficial properties such as a low toxicity (Beyer et al.1987, Sommer et al.1990, Quintanar-Guerrero et al.1996, Das et al.2017) as well as low viscosity, but also partial water miscibility (Shaikh and Sivaram 1996). This gap in water miscibility enables the formation of emulsion droplets which act as precursor templates for microspheres.