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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
Most of the work with 31P in AD has focused on pathological changes in the brain (1986, 1987, 1988, 1989), although there have been recent in vivo studies done by Pettegrew et al. (in press). The first in vitro autopsy studies were done by Barany et al. who showed an elevation of glycerophosphorylcholine compared to glyceryolphosphorylethanolamine. Wurtman et al. (1989) with chemical methods, verified the finding of increased brain glycerophosphorylcholine in AD.
Nature, Function, and Biosynthesis of Surfactant Lipids
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Recently, an alternative pathway known as the CDP-choline-dependent glycerophosphorylcholine synthesis has been proposed by Infante,183,184 mainly on the basis of theoretical considerations. More precisely, based on a critical appraisal of available data, it was postulated that the CDP-choline and the deacylation-reacylation pathways cannot quantitatively account for the synthesis of DPPC. The alternative pathway would branch from the major CDP-choline pathway at the level of CDP-choline to form de novo glycero-3-phosphorylcholine (GPC) by condensation with glycerol-3-phosphate under the action of GPC synthetase activity. Subsequently, GPC would be acylated specifically with palmitoyl-CoA in two steps to form palmitoyl-lysoPC and finally DPPC.
Other Toxic Effects
Published in Lars Friberg, Tord Kjellström, Carl-Gustaf Elinder, Gunnar F. Nordberg, Cadmium and Health: A Toxicological and Epidemiological Appraisal, 2019
In a series of experiments on rats, Kopp and co-workers140-143 were able to demonstrate certain effects of cadmium on the myocardium in addition to hypertension. In rats given 5 mg Cd per liter in drinking water for 24 weeks, ECG recordings differed significantly from controls in several characteristics; e.g., the PR interval was lengthened and the ventricular depolarization time (QS interval) was prolonged in cadmium-exposed rats. Electrograms of “His’s bundle” revealed a 30% increase in the A-H interval. In heart tissue homogenates from exposed animals, the content of ATP was lowered compared to controls.140 In later similar experiments141,142 a marked decrease in the content of glycerophosphorylcholine was also found in exposed rats. The data indicate a depressive effect of cadmium on the heart. The cadmium content in heart muscles from exposed rats has been in the order of 0.1 mg/kg compared to about 0.01 mg/kg in controls. Corresponding concentrations of cadmium in kidney were in the order of 30 to 40 mg/kg in exposed rats compared to less than 0.1 mg/kg in controls.142 In 1983, Kopp et al.144 reported similar cardiovascular changes in rats given a lower dose of cadmium, 1 mg/ℓ in drinking water.
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).
Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss
Published in Gut Microbes, 2021
Florian Seyfried, Jutarop Phetcharaburanin, Maria Glymenaki, Arno Nordbeck, Mohammed Hankir, Jeremy K Nicholson, Elaine Holmes, Julian R. Marchesi, Jia V. Li
Bile acids are believed to play a key role in achieving metabolic benefits of RYGB surgery.37 However, while the majority of studies in animal models and patients have shown a surge in plasma BA levels postoperatively,38,39 others reported no change40 or even a reduction.41 Similarly, fecal bile acids have been shown to markedly decrease in patients and rats after RYGB,6,42,43 raising the question of the role of luminal bile acids in regulating metabolic function. In this study, we showed that BA levels in portal vein were higher compared to peripheral blood in all three groups of animals, with the highest number of disturbed BAs in Sham-BWM, suggesting caloric restriction has a greater impact on BA composition. Three BAs, namely, 3α-hydroxy-12-ketolithocholic acid, taurochenodeoxycholic acid, and tauro-β-muricholic acid were found to be higher in portal vein blood in both RYGB and Sham-BWM groups compared to their systemic levels, which could be due to reduced food intake following the surgery. Moreover, primary BAs such as cholic acid and chenodeoxycholic acid, and secondary BAs, mainly taurine-conjugated BAs (e.g., taurohyodeoxycholic acid and taurochenodeoxycholic acid) were present at lower levels in RYGB compared to Sham-operated groups, which is consistent with the observations in a mini-pig model post-RYGB.44 Notably, ileal conjugated bile acids are also lower in RYGB-operated compared to Sham-obese rats,45 suggesting that their increased deconjugation by ileal microbiota account for their decreased reabsorption into the enterohepatic circulation. Simonen and colleagues39 showed that despite total serum BA levels increasing post RYGB, levels of conjugated BAs, specifically taurine-conjugated BAs, decreased and this change was associated with increased lipid oxidation at the expense of glucose oxidation. This data corroborates our observations of reduced plasma lipids and glycerophosphorylcholine. FXR signaling, mainly activated by chenodeoxycholic acid, modulates BA synthesis, lipid metabolism, glucose homeostasis, and inflammation.46 Taurine-conjugated BAs are the most potent activators of TGR5 receptor.46 TGR5 signaling is implicated in energy balance, GLP-1 secretion, glucose metabolism and insulin sensitivity.11,47 However, the reduction of plasma BA levels observed in our study may suggest that the axis of BAs and TGR5/FXR signaling may not be the key mechanism, through which RYGB improves glucose tolerance and insulin sensitivity in Zucker obese rats, which is in agreement with a previous study carried out using TGR5-/- mice.48 A growing body of evidence suggests that temporal changes in BA levels could be unrelated to glycemic control early after gastric bypass.49 Furthermore, disruption of enterohepatic circulation using BA sequestrants50 or inhibitors of BA transporters51 resulting in reduced plasma BAs and increased fecal excretion nonetheless improved glucose metabolism.