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CT, MRI, and NMR Spectroscopy in Alzheimer Disease*
Published in Robert E. Becker, Ezio Giacobini, Alzheimer Disease, 2020
Liane J. Leedom, Bruce L. Miller
Pettegrew reported extensive changes in phosphomono and phosphodiesters of choline and ethanolamine in the brains of patients with AD with in vivo NMR spectroscopy (Pettegrew In Press). Specifically, he found that in addition to glycerophosphorylcholine and glycerophosphorylethanolamine that, phosphorylcholine and phosphorylethanolamine were elevated in AD brains. Pettegrew notes that the phosphomonoesters are anabolic building blocks necessary for the production of brain phospholipids and their accumulation could mean a metabolic block. Conversely, it might mean that there was an excessive degradation of the diesters by phospholipase C although this has not been demonstrated in chemical studies (Kanfer et al., 1987).
Role of Monoclonal Antibodies in Understanding the Interactions Between Anti-Phospholipid Antibodies and Phospholipids
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
A, but selected for reactivity with liposomes containing the immunizing lipids but lacking lipid A.33 The antibody reacted best with liposomes containing the original immunizing mixture but also reacted with liposomes containing other forms of phosphatidylcholine (dimyristoyl phosphatidylcholine, or egg phosphatidylcholine) but not dipalmitoyl phosphatidylethanolamine. The antibody reactivity was inhibited by phosphorylcholine, the polar head group of phosphatidylcholine, and partially by phosphorylated and sulfated molecules. Banerji et al.33 suggest that it is possible that lipid A helps to hold the phosphatidylcholine in the exact configuration required for optimal antibody binding, as lipid A is known to influence the fluidity of lipid bilayers. In a recent review, Alving suggested that antibodies induced by liposomes containing lipid A recognized a phosphate ester epitope shared by lipid A, cardiolipin, DNA, polynucleotides and lipoteichoic acids from Gram-positive bacteria.34 Accordingly, Alving has put forth the hypothesis that antibodies induced by lipid bilayers containing lipid A may be the primary immunological event which results in the appearance of antibodies reactive with DNA, polynucleotides, lipoteichoic acids and even certain sulfated lipids.34 (For further discussion of this subject, see Chapter 4.)
Biochemical Aspects of Fatty Liver
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Phospholipids in lipoproteins are mostly represented by lecithins and cephalins, as well as by inositolphosphate derivatives. Lecithins are esters of glycerol, where two of the hydroxyls are esterified by fatty acids, whereas the third one is bound to phosphorylcholine. In cephalins, phosphorylcholine is substituted by either phosphorylserine or by phosphorylethanolamine. Lecithins, due to the presence of choline, are much more polar than cephalins. Choline deficiency is one of the most studied forms of experimental fatty livers. It can obtained by two main methods: long-term feeding on a diet devoid of choline (Best and Hershey, 1932; Best and Channon, 1935; Best et al., 1936, 1949), or by force-feeding of young Sprague-Dawley rats on a diet containing a high level of fat and at the same time deficient in choline (Lombardi, 1966; Lombardi et al., 1964, 1966). These rats usually double their weight in a week, when they are about 150 g, and have, therefore, higher needs for choline than most animals; moreover, the high-fat intake increases the need for choline.
Orally administered intelligent self-ablating nanoparticles: a new approach to improve drug cellular uptake and intestinal absorption
Published in Drug Delivery, 2022
Yanzi Liang, Ruihuan Ding, Huihui Wang, Lanze Liu, Jibiao He, Yuping Tao, Zhenyu Zhao, Jie Zhang, Aiping Wang, Kaoxiang Sun, Youxin Li, Yanan Shi
Oral drug administration is the most commonly used method of drug administration as the drugs used during the method are portable. The harsh acidic environment of the stomach, extensive enzymatic degradation in the presence of various enzymes, and the process of mucus clearance reduce the efficiency of the method (Fan et al., 2018). Therefore, nanocarriers designed for oral administration should be able to promote mucus permeation and epithelial absorption, although these two processes require significantly different carrier properties (Liu et al., 2016; Drucker, 2020). Hence, oral drug delivery systems are being increasingly studied. Commonly used Polyethylene glycol-modified nanoparticles have hydrophilic and near-neutrally charged surfaces that reduce the mucus adhesion by hindering hydrophobic or electrostatic interactions (Khutoryanskiy, 2018; Nie et al., 2019). It has been recently reported that a zwitterionic carrier platform can be used to simultaneously surmount the mucus and epithelial barriers. The use of zwitterions significantly increases the rate of protein payload transport. Moreover, the zwitterionic systems do not exhibit immune response, unlike Polyethylene glycol (PEG) (Xu et al., 2018; Debayle et al., 2019; Han et al., 2020). Zwitterionic polymers that are electrically neutral but bear identical cationic and anionic groups have attracted immense attention from researchers working in the field of biomedicine. Phosphorylcholine, carboxybetaine, and sulfobetaine are the most widely used systems (Peng et al., 2020; Bevilacqua et al., 2021).
Biomarkers of disease in human nails: a comprehensive review
Published in Critical Reviews in Clinical Laboratory Sciences, 2022
Sarahi Jaramillo Ortiz, Michael Howsam, Elisabeth H. van Aken, Joris R. Delanghe, Eric Boulanger, Frédéric J. Tessier
In another small, case-control study on breast cancer (10 cases, 12 controls), Mitruka and colleagues [64] reported an absence of the free amino acids tryptophan, tyrosine, phenylalanine, and histidine in cases’ nails. They applied a novel vertical tube gel electrophoresis (VTGE) separation method to nail lysates before analysis with high-resolution, quadrupole/time-of-flight mass spectrometry (Q-TOF-MS). Phenylalanine was the most abundant of the free amino acids in nails from controls, making its absence among cases the more remarkable. The authors draw upon a significant amount of work describing altered free amino acid profiles in the circulation of cancer patients (e.g. [65]) and proposed that this results from both local and generalized metabolic reprogramming by tumors that enhance catabolism of free amino acids. Although still in the pre-print stage at the time of writing this review, these researchers also reported that their VTGE/Q-TOF-MS approach revealed an absence of the lipid metabolites choline, phosphorylcholine, and lyso-phosphatidylcholine in nails from the same population of breast cancer cases [66]. Again, their small (and as-yet-unpublished) study is bolstered by the relatively well-described alterations of lipid metabolism in cancer (e.g. [67]). Both the VTGE/Q-TOF-MS approach and the preliminary findings from these studies require further confirmation, but they merit inclusion here for their innovation and the exciting potential they offer for analyzing molecular biomarkers of cancer in nails.
Sialylated milk oligosaccharides alter neurotransmitters and brain metabolites in piglets: an In vivo magnetic resonance spectroscopic (MRS) study
Published in Nutritional Neuroscience, 2021
Hong Xin Wang, Yue Chen, Ziaul Haque, Michael de Veer, Gary Egan, Bing Wang
The absolute concentrations of 33 brain metabolites including alanine (Ala), aspartate (Asp), Cr, Cho, γ-aminobutyric acid (GABA), glycerophosphorylcholine (GPC), d-Glucose (Glc), glutamine (Gln), glutathione (Glth), glutamate (Glu), lipid (Lip) (09, 13a, 13b, 20), macromolecular (MM) (09, 12, 14, 17, 20), NAA, N-acetylaspartylglutamate (NAAG), myo-inositol (mIns), lactate (Lac), phosphorylcholine (PCh), phosphocreatine (PCr), scyllo-inositol (SI) taurine (Tau), total NAA (TNAA), total choline (TCho), total creatine (TCr), total lipid and macromolecular (TLM) were detected and automatically analysed at TE 270 ms between the three piglet groups using TARQUIN software. The mean absolute concentration of 33 metabolites in 3 different groups of 38 d-old piglet is shown in Figure 4. An astrocyte marker [19] and essential part of the inositol triphosphate intracellular second messenger system [20] of mIns was higher in both SL/SLN (22.11 ± 1.12 mM) and SL (19.02 ± 1.13 mM) compared with the control (17.75 ± 1.13 mM). The overall difference between the three groups was statistically significant (P = .031, Figure 4). These differences were even more significant when the data was analysed after adjustment for volume of whole brain, white matter, grey matter, brain weight or body weight gain as covariates (P = .029), or when comparing the relative concentration for mIns using the ratios of mIns/NAA, mIns/Cho and mIns/Cr with or without adjustment for volume of whole brain, white matter, grey matter, brain weight or body weight as covariates (Supplemental Table 2).