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Pseudo-Proteins and Related Synthetic Amino Acid-Based Polymers Promising for Constructing Artificial Vaccines
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Highly promising representatives of the synthetic AABPs, having valuable material properties and suitable for biomedical applications, were first reported in 1994 (Arabuli et al. 1994). Along with AAs the main “bricks” for constructing these polymers were physiological, non-toxic, cheap, and readily available organic compounds such as diols and dicarboxylic acids. We used the name pseudo-proteins (PPs) for these polymers to distinguish them from other classes of the synthetic AABPs (Katsarava, Kantaria, and Kobauri 2019).
Multiple acyl CoA dehydrogenase deficiency/glutaric aciduria type II ethylmalonic-adipic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The diagnosis in all forms of multiple acylCoA dehydrogenase deficiency has usually been made on the basis of the unusual pattern of organic acid excretion in which a large number of organic acids are found in elevated amount in the urine. This is especially true in the severe neonatal onset form in which the quantities found are enormous. The most prominent of these are lactic acid and glutaric acid, but a large number of other dicarboxylic acids and hydroxy acids are found. Among the former are ethylmalonic, adipic, suberic, and sebacic acids, as well as unsaturated suberic acids. Among the latter are 2-hydroxybutyric, 2-hydroxyglutaric, and 5-hydroxyhexanoic acids. 3-Hydroxyisovaleric and 2-hydroxyisocaproic acids are also found in the urine. Most of the same organic acids are found in increased amounts in the plasma. The concentrations of glutaric and lactic acids are prominent. p-Hydroxyphenyllactic acid may be elevated in the blood and the urine, possibly an index of immaturity or of hepatic disease.
Cholinergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Vishal S. Gulecha, Manoj S. Mahajan, Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
Atropine is found with hyoscyamine in A. belladonna. Hyoscyamine readily hydrolyzes to atropine in aqueous alcohol. Therefore, atro-pine is a naturally occurring alkaloid in the form of a racemic mixture of d- and l-hyoscyamine in equal parts (Finar, 1965). It was found that upon hydrolysis, atropine gave (±)-tropic acid (C9H10O3) and tropine (C8H15ON), which was shown to be alcohol. The presence of hydroxyl group in the structure of tropine makes it a saturated compound. On the other hand, dicarboxylic acid derivative of tropine, the tropinic acid contains the same number of carbon atoms as that of tropine (Rang and Dale, 2007; Shrivastava, 2017).
Variable sensitivity to diethylene glycol poisoning is related to differences in the uptake transporter for the toxic metabolite diglycolic acid
Published in Clinical Toxicology, 2023
Julie D. Tobin, Courtney N. Jamison, Corie N. Robinson, Kenneth E. McMartin
Diglycolic acid is a 4-carbon dicarboxylic acid, similar in structure to the citric acid cycle intermediate, succinate. Succinate is taken into kidney cells by the SLC13 family of solute carriers known as the sodium dicarboxylate transporters (NaDC-1 and NaDC-3) [18]. Sodium-dependent dicarboxylate transporter-1 has broad substrate specificity, with preference for four carbon dicarboxylates, such as succinate and possibly DGA. Previous studies using human proximal tubule (HPT) cells in culture have shown that treatment with a small molecule inhibitor of NaDC-1 markedly reduced the uptakes of both succinate and DGA [11]. Also, the uptake of succinate and the toxicity of DGA were reduced in cells pre-treated with siRNA to knockdown NaDC-1 function. Lastly, DGA reduced the uptake of succinate by these cells. Parallel studies examining the role of NaDC-3 were not definitive for a role of NaDC-3 in DGA uptake. Taken together, these studies indicate that DGA is likely taken into kidney cells by the NaDC-1 transporter. Hence for this study, we have specifically focused on differences in NaDC-1 transporter expression.
Recent advancements in cellulose-based biomaterials for management of infected wounds
Published in Expert Opinion on Drug Delivery, 2021
Munira Momin, Varsha Mishra, Sankalp Gharat, Abdelwahab Omri
Synthetic polymers are widely used as a material for wound dressing owing to their ease of manufacture and high availability. Advanced dressings are usually made of polymeric materials, which can provide a suitable wound environment and also serve as a carrier for drug delivery. Synthetic Polymers like poly(vinyl pyrrolidone), poly(lactide-co-glycolide), poly(hydroxyalkyl methacrylates), and poly(vinyl alcohol) are frequently employed in wound dressing [78]. In the case of synthetic polymers, poor biocompatibility and release of acidic degradation product (Dicarboxylic acid monomers) due to hydrolysis can be an issue. Moreover, natural polymers are similar to human ECM and are thus readily recognized and accepted by the body. They have many benefits, including natural abundance, apparent ease of isolation and scope for chemical alteration to suit technical needs [79]. These properties make natural polymers preferable over synthetic polymers.
Neurotoxic effects of nephrotoxic compound diethylene glycol
Published in Clinical Toxicology, 2021
Courtney N. Jamison, Robert D. Dayton, Brian Latimer, Mary P. McKinney, Hannah G. Mitchell, Kenneth E. McMartin
Despite the variability in toxicity among similarly-dosed rats, toxicity was only observed when there was accumulation of DGA within target tissues. Hence, this variability in DEG toxicity suggests some unevenness in the processing of DGA, either in its formation from DEG or its uptake and accumulation in tissues. The Wister-Han rat used in these studies is an outbred strain, or genetically diverse within the population, so DEG metabolism via alcohol dehydrogenase and aldehyde dehydrogenase, as well as a variability in DGA transporter activity could potentially affect the accumulation of DGA in target tissues [31,32]. Ethanol consumption studies in rats show that there is a low correlation between alcohol consumption and sensitivity to ethanol, and that genetic differences in alcohol and/or aldehyde dehydrogenase activities play a role in this difference just like in humans [33]. Because of the similarity of DGA’s four carbon dicarboxylate structure with that of succinate [18], apical sodium dicarboxylate (NaDC)-1 and basolateral NaDC-3 transporters are suspected to be involved in DGA uptake into the proximal tubule cell. Because dicarboxylic acids are also effluxed from the proximal tubule cell in exchange for organic acids via the organic acid transporters (OATs), DGA could be effluxed by these same transporters. Individual variation in the activity of either the uptake or the efflux transporters could lead to differential accumulation of DGA by the proximal tubule cell and thus to individual sensitivity to DEG toxicity.