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Aciclovir and Valaciclovir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Renee-Claude Mercier, Gregory Mertz
To improve on the poor oral bioavailability of aciclovir, 18 amino acid esters of aciclovir were synthesized and tested by GlaxoSmithKline (Beauchamp et al., 1992). The l-valyl ester, valaciclovir hydrochloride, resulted in highest oral bioavailability of aciclovir (Crooks and Murray, 1994). Valaciclovir is absorbed by intestinal dipeptide transporters, including human intestinal peptide transporter 1 (hPEPT-1), followed by hydrolysis of valaciclovir to aciclovir by esterases in the gut lumen, intestinal wall, and liver (Kim et al., 2003; MacDougall and Guglielmo, 2004; Lai et al., 2008; Figure 213.3).
Endocytosis of ATB0,+(SLC6A14)-targeted liposomes for drug delivery and its therapeutic application for pancreatic cancer
Published in Expert Opinion on Drug Delivery, 2020
Longfa Kou, Huirong Huang, Xinlu Lin, Xinyu Jiang, Yi Wang, Qiuhua Luo, Jin Sun, Qing Yao, Vadivel Ganapathy, Ruijie Chen
Plasma membrane transporters are cell-surface proteins that are responsible for uptake of nutrients, including glucose, amino acids, and vitamins, and also for removal or secretion of specific metabolites and xenobiotics [20]. To date, more than 400 transporters have been identified in mammalian cells; these transporters are classified into two large classes, namely solute carriers (SLCs) and ATP-binding cassette (ABC) transporters. To support the malignant growth and development, tumor cells always selectively upregulate some transporters in the plasma membrane to increase nutrient absorption, therefore providing differentially expressed targets for drug delivery [20–23]. Interestingly, the transporters that are overexpressed for this purpose are not the same in all cancers. They vary depending on the type of tumor, which further accentuates the specificity in terms of differential expression of these cell-surface proteins among different cancer types. In recent years, there has been a surge of studies exploiting such differentially expressed transporters on tumor cells as targets for improved delivery of anticancer drugs. For example, Guo et al. [24] constructed a nanopompon with surface conjugation of dehydroascorbic acid for tumor-cell specific delivery of anti-miR21. This nanopompon was able to target the glucose transporter 1 (GLUT1, SLC2A1) that is overexpressed several-fold in tumor cells than in normal cells, thereby selectively facilitating drug delivery to tumors. The other transporters that have been exploited in a similar way include system L amino acid transporter 1 (LAT1, SLC7A5) [25,26], choline transporter 1 (ChT1, SLC5A7) [27], peptide transporter 1 (PepT1, SLC15A1) [28], and organic cation/carnitine transporter 2 (OCTN2, SLC22A5) [10,29].
Protective effects of di- and tri-peptides containing proline, glycine, and leucine on liver enzymology and histopathology of diabetic mice
Published in Archives of Physiology and Biochemistry, 2022
Mehran Mesgari-Abbasi, Hadi Valizadeh, Navideh Mirzakhani, Tohid Vahdatpour
In the gastrointestinal tract, Small peptides especially dipeptides and tripeptides are also absorbed into circulation by peptide transporter 1 (PepT1). More than 30 peptides (mainly dipeptides and tripeptides) have been identified in blood after consumption of the rich sources of protein and peptides such as gelatin (Song and Li 2017). Di- and tripeptides have nutritional value, because its uptake rate is higher than that of free amino acids and efficiently utilized for metabolism or may have specific bioactivities as quasi-hormones (Vahdatpour et al. 2019).
Invariant natural killer T cells minimally influence gut microbiota composition in mice
Published in Gut Microbes, 2022
Qiaochu Lin, Meggie Kuypers, Zhewei Liu, Julia K Copeland, Donny Chan, Susan J Robertson, Jean Kontogiannis, David S Guttman, E. Kate Banks, Dana J Philpott, Thierry Mallevaey
Cross-fostering is a simple and effective method for generating mice with a desired gut microbiota. Multiple studies have demonstrated that newborn pups fostered by dams with a different microbiota develop the same microbiota and associated phenotypes as their nursing mother rather than their birth mother.46,64,73,74 In line with this, cross-fostering of our SPF CD1d-deficient mice with surrogate mothers in barrier conditions effectively eliminated several microbes that are known to alter the microbiota and immune landscape,27,28,44,45,75–78 and engrafted the mice with a new conventional microbiota from which we could then track how it is selectively shaped by CD1d and/or iNKT cells over time. However, a question that may arise from experiments that study the impact of host genetics on the microbiota is how long should the microbiota be monitored to determine whether a genotype effect becomes biologically relevant? In this study, we examined the microbiota composition of littermate mice at 7 to 8 weeks of age to match with previous studies that reported the age of the mice used.39–42 While we found that the effect of genotype on microbiota was indeed statistically significant, it was minimal compared with other non-genetic factors. Consistent with our finding, a recent study by Viennois et al. demonstrated that the influence of peptide transporter 1 (PepT1) deficiency on the microbiota is minimal between F1 PepT1+/+ and PepT1−/− littermates.79 The effect of PepT1 gradually emerged along with its associated phenotypes after several generations of separate homozygous breeding of PepT1+/+ and PepT1−/− mice from the initial intercross, which suggests that certain gene mutations may take longer to exert their effect on the microbiota.79 However, a limitation of such experimental design is that it becomes unclear whether the ecological drift in the microbiota is driven by the genotype or randomly introduced by adjacent breeding. Our work showed that the microbiota of our WT mouse colony can shift over time despite consistent housing conditions and absence of genetic manipulation. This is likely due to random breeder selection, wherein certain inherent microbiota differences within and between breeding pairs are selectively propagated through their progeny, ultimately leading to a change in the microbial landscape of the entire colony.80 Therefore, any microbiota changes observed in a gene-targeted mouse line that is bred and maintained in isolation must be interpreted with care in order to determine the true effect of the host genetics. Nevertheless, we cannot exclude the possibility that the influence of CD1d and/or iNKT cells may increase with age, and hence the microbiota of older CD1d littermate mice may warrant further examination in subsequent studies. In addition, it is also possible that iNKT cell deficiency could impact microbiota resilience (i.e. the ability to recover from perturbations), which has been associated with better health.81 In line with this, Nod2-/- mice have altered and/or delayed microbiota recovery after antibiotic treatment, which impacts colitis susceptibility.82,83