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Fenugreek
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Ujjwala Kandekar, Sunil Ramdasi, Prasad Thakurdesai
It is the free amino acid found specifically in selected plants of the Trigonella genus. It comprises nearly up to 80% of the total amino acids (0.015–0.4%) of fenugreek seeds (Hajimehdipoor et al. 2010). It is derived from isoleucine hydroxylation and exists in two isomeric forms, and major fraction constitutes 2S, 3R, 4S while the minor exhibits 2R, 3R, 4S configuration. Optical rotation yields a value of [αD] + 30.5 (c = 1, H2O), [αD] + 31 (c = 1.1, H2O). It is available as white powder or flakes. The melting point is 223.5 °C. The molecular weight is 147.1 as per the mass spectrometric evaluation (Hari and Mohan 2014). Under acidic conditions, the linear form may convert to lactone form. The linear form of isoleucine is biologically active. In S-confirmation, full methylation at carbon-α and carbon-γ hydroxylation are essential for insulinotropic activity (Broca et al. 2000).
Field Trials of Food Fortification with Iron: The Experience in Chile
Published in Bo Lönnerdal, Iron Metabolism in Infants, 2020
Tomás Walter, Manuel Olivares, Eva Hertrampf
Amino acid analysis (Table 6) demonstrates that in comparison to the control cookies, the fortified cookie had a higher value for all essential amino acids except isoleucine. A significant difference between the fortified and unfortified cookies was that lysine was 73% deficient in the unfortified cookie and only 8% deficient in the fortified cookie. As a result, the amino acid score of the unfortified cookie was 28.6 and that of the fortified cookie 40.3, with isoleucine as the first limiting amino acid. Isoleucine is very abundant in cow’s milk; therefore, when the fortified cookies are consumed simultaneously with cow’s milk or a milk substitute, the amino acid score of the meal increases markedly.
Nutrition
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Proteins are required in the diet to replace the protein lost continuously by catabolism – approximately 200 – 400 g protein per day. Although amino acids formed by protein breakdown are reutilized, an additional protein intake of 20–40 g/day is required to maintain protein balance. Amino acids such as isoleucine, leucine, valine, lysine, methionine, threonine, phenylalanine and tyrosine are called essential amino acids because the body cannot synthesize them from other amino acids by transamination. Sulphur-containing amino acids, cysteine and methionine, provide the sulphur contained in proteins and other biologically important compounds and are the source of sulphates in urine. The caloric value of protein is 4 kcal/g. It is recommended that the daily diet should contain 1 g of protein per kilogram of body weight to allow for the great variation in the minimal needs of individuals. Newborns require approximately five times as much protein as an adult for growth.
In vitro drug-drug interactions of decitabine and tetrahydrouridine involving drug transporters and drug metabolising enzymes
Published in Xenobiotica, 2022
Carolina Säll, Christian Fogt Hjorth
Clinical concentrations of decitabine and tetrahydrouridine for the treatment of SCD, which can be used to guide concentration selection in the current in vitro DDI studies, have previously been published as part of a first-in-human trial where a fixed oral tetrahydrouridine dose (10 mg/kg) was administered 60 min before oral decitabine (0.01–0.16 mg/kg) (Molokie et al. 2017). The highest measured decitabine concentration in plasma that resulted in DNMT1 depletion and upregulation of HbF was ∼50 nM, which was measured 2 h after the 0.16 mg/kg decitabine dose. However, as pharmacokinetic (PK) sampling was not extensive (i.e. 0, 2, 4, and 24 h after the first decitabine dose), the maximum plasma concentration (Cmax) was not optimally determined from a PK perspective and thus could be underestimated due to the low number of samples. In a recently completed Phase I study designed to investigate the effect of a high-fat, high-calorie meal on the PK of NDec (NCT04086238), healthy adults received similar doses of decitabine and tetrahydrouridine as in the first-in-human study (males: 0.188 mg/kg decitabine and 9.4 mg/kg tetrahydrouridine; females: 0.22 mg/kg decitabine and 11 mg/kg tetrahydrouridine). This resulted in a geometric mean decitabine Cmax of 0.12 µM (male subjects) and 0.13 µM (female subjects). The mean tetrahydrouridine Cmax was ∼5 µM. Unbound Cmax is not expected to differ substantially from total Cmax as plasma protein binding is negligible for decitabine and tetrahydrouridine (Beumer et al. 2008a; EMA 2019).
The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications
Published in Expert Review of Clinical Immunology, 2021
Filipe Seguro Paula, José Delgado Alves
The first in-human study using an anti-Notch mAb was with brontictuzumab [90], but again the gastrointestinal side effects were considerable, especially with the chronic use. Several others have been developed, mainly targeting the ligand-binding extracellular domains of the Notch receptors. It is noteworthy that one of them, by targeting specifically Notch1, averted the gastrointestinal toxicity in a preclinical study, supposedly by leaving the Notch2 signaling intact [89]. The same logic applies to a mAb against Notch-3, which would not produce goblet cell hyperplasia and diarrhea, as those effects are dependent on Notch-1/Notch-2 signaling. However, gastrointestinal side-effects still existed, including nausea and abdominal pain in up to 25% of participants of a phase I clinical trial [91], despite being reportedly well tolerated. Notch-3 inhibition could be helpful in patients with SSc as it is one of the two most important receptors in myofibroblasts and vascular smooth muscle cells.
Surface atomic arrangement of nanomaterials affects nanotoxicity
Published in Nanotoxicology, 2021
Kaiwen Li, Zhongwei Wang, Hui Zeng, Jing Sun, Yue Wang, Qixing Zhou, Xiangang Hu
Metabolomics analysis provides a global view of the biological response to external stimuli (Krivitsky et al. 2019; Grintzalis et al. 2019). Branched chain amino acids (BCAAs) such as valine, leucine, isoleucine and threonine play a crucial role in skeletal muscle, affecting muscle morphology and function in living organisms (Wang et al. 2016). The main function of the aminoacyl-tRNAs is in protein synthesis (Raina and Ibba 2014). Compared to 1 T-MoS2, 2H-MoS2 upregulated BCAAs biosynthesis and aminoacyl-tRNA biosynthesis, indicating a stress response (Figure 6). Arginine is a nutritionally essential amino acid for embryonic survival and maintenance of vascular tone (Wu et al. 2009), and downregulated by both 1 T-MoS2 and 2H-MoS2. Compared to 1 T-MoS2, 2H-MoS2 downregulated glyoxylate and dicarboxylate metabolism, where glyoxylate and dicarboxylate metabolism are energy metabolism processes (Germain et al. 2017), explaining the higher toxicity of 2H-MoS2.