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Prednisolone
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Prednisolone base is virtually always used as tablet, which implies that by far most allergic reactions to ‘prednisolone’ have in fact been the result of sensitization to an ester of prednisolone or of cross-reactivity to another corticosteroid. It is also likely that there has been confusion in some publications on the correct forms of the drugs used, e.g. that prednisolone was mentioned where in fact an ester form should have been mentioned.
Neurological problems
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
Anaesthetic agents: Women with MG are more resistant to the depolarizing neuromuscular blocking agents such as succinyl choline and therefore these women require higher doses to achieve the same degree of muscle relaxation. By contrast, women with MG are extremely sensitive to non-depolarizing muscle relaxants (e.g. suxamethonium), which may have an exaggerated or prolonged effect. Consultation with an experienced obstetric anaesthetist is essential, preferably prior to delivery.Epidural analgesia and anaesthesia are safe to use, but the ester type of local anaesthetics (e.g. chloroprocaine, tetracaine) depend on maternal plasma cholinesterase for their metabolism and should be avoided if the mother is being treated with anticholinesterases.Lignocaine and the amide type of local anaesthetics are metabolized by a different pathway and are therefore safe for use in labour and delivery.Epidural analgesia is preferable to general anaesthesia whenever possible. If an inhalational anaesthetic is required, ether and halothane should be avoided.
Oncogenic DNA Viruses
Published in Pimentel Enrique, Oncogenes, 2020
Tumor initiators and promoters such as phorbol diester (TPA) may enhance EBV replication in cultures of human lymphoblastoid cells.12 The expression of a gene, or genes, located in a specific region of the EBV genome is required for the initiation of EBV replication, whereas expression of genes located in other regions of the viral genome are important for the establishment of lymphocyte immortalization.13 A specific region of the EBV genome (the 0.26 to 0.36 region) is necessary for the initiation of EBV-induced cellular transformation but may be dispensable for the maintenance of a transformed phenotype.14 EBV is the only known mitogen for human B-lymphocytes which acts independently of factors produced by accessory cells, including cytokines produced by T-cells. Following EBV-induced transformation, B-lymphoblasts release a soluble factor which mimics the B-cell stimulatory products of mitogen-conditioned T-lymphocytes and, apparently, the virally transformed cells utilize this activity to sustain their own growth.15
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Structure-activity relationship studies demonstrated that macrocyclic diester PAs are more mutagenic and carcinogenic than open-chain diesters followed by monoesters and necine bases (Hincks et al. 1991; Kim et al. 1993). The stereochemical orientation of the ester linkage (i.e. retronecine-type vs heliotridine-type) has no effect on DNA or protein cross-linking as well as biological activity. GSH conjugation is generally considered as a detoxification pathway, however, reaction of 7-GSH-DHP with dG and dA produced four DNA adducts, DHP-dA-3, DHP-dA-4, DHP-dG-3 and DHP-dG-4 adducts suggesting that formation of DHP-GSH conjugates may serve as potential activation pathways leading to liver tumor initiation (Xia et al. 2015). Relatively stable GSH conjugates may be able to survive long enough to reach target organs downstream from the liver to elicit extrahepatic toxicity. This resembles the formation of GSH − NAPQI ipso adduct which can migrate from its site of formation (i.e. liver) to extrahepatic cell compartments where it can be readily reversible back to NAPQI leading to toxicity (Chen et al. 1999). Further studies are warranted as to the role of these secondary metabolites in PA-induced tumorigenicity. On the other front, depending on the PA types and chemical structures, more stable pyrrolic esters with longer half-lives may also be able to reach target organs to induce extrahepatic toxicities (Cooper and Huxtable 1999).
A review of phthalate pharmacokinetics in human and rat: what factors drive phthalate distribution and partitioning?
Published in Drug Metabolism Reviews, 2019
Elena Domínguez-Romero, Martin Scheringer
Phthalates are metabolized in different tissues in human and rat, including intestine, liver, and plasma (see Supplementary material section 10.2) (Shintani 2000). The pathways of metabolism of phthalates in human and rat are explained in the Supplementary material (see section 10.1, Tables S37–S46). These pathways were previously reviewed by Frederiksen et al. (2007). Briefly, the diester phthalates are firstly hydrolyzed to monoesters, which are generally further glucuronidated and/or oxidated. The metabolic pathways depend on the physico-chemical properties of phthalates and are simpler for less hydrophobic phthalates with lower molecular weight (i.e. DEP) than for more hydrophobic ones. Between human and rat, the differences in metabolic pathways are quantitative, rather than qualitative.
An updated patent review of Nrf2 activators (2020-present)
Published in Expert Opinion on Therapeutic Patents, 2023
Ziquan Zhao, Ruitian Dong, Keni Cui, Qidong You, Zhengyu Jiang
Dimethyl fumarate (DMF, 1, Figure 3), a methyl ester derivative of fumaric acid isolated from the plant Fumaria officinalis, is the most successful electrophilic Nrf2 activator [78]. DMF has been considered as a prodrug, which can be hydrolyzed to monomethyl fumarate (MMF, 2, Figure 3) by esterases [79]. In general, the diester DMF with high permeability tends to have better biological effects in in vitro models compared to its monoester MMF. However, some researchers asserted that MMF is the main active component after oral treatment with DMF in in vivo models [80,81]. DMF and its metabolite MMF exhibit outstanding anti-inflammatory, antioxidant, and Nrf2 activation effects owing to the presence of α,β-unsaturated carbonyl part, which can form the Michael addition with the cysteine thiol residue of Keap1 [82]. In 2013, DMF had been approved by the Food and Drug Administration (FDA) as a new oral therapeutic drug for the treatment of relapsing forms of multiple sclerosis (MS) [83,84]. Importantly, Amaravadi et al. [85] disclosed the evidence of Nrf2 pathway activation in DMF-treated MS patients from Phase III studies. In addition, beneficial therapeutic effects of DMF were also found in cellular or animal models of other inflammatory and neurodegenerative diseases [86,87]. It is noteworthy that DMF can also exert its effects via modulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway, hydroxycarboxylic acid receptor 2 (HCAR2) and AMP-activated protein kinase-sirtuin 1 (AMPK-Sirt1) pathway [81]. Since 2020, DMF has undergone many new clinical trials for other therapeutic applications, including acute ischemic stroke, age-related macular degeneration, and intracerebral hemorrhage, which are summarized in Table 1.