Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile

Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patients with pigment stones. Gel chromatography was used to separate vesicles and micelles in the native bile with an eluting buffer containing 10 mM sodium cholate to prevent disruption of micellar lipids. Cholesterol, phospholipid and bile salt concentrations were measured in every fraction collected. Bile acid, phospholipid, cholesterol and total lipid concentrations were not significantly different in samples with and without cholesterol crystals. The cholesterol saturation index (1.4 ± 0.11 vs. 1.0 ± 0.08) was significantly (p < 0.01) higher in biles with crystals than without crystals. Gel filtration revealed a vesicular peak in addition to micellar fraction in 18 (23.1 ± 3.2% of total cholesterol) of the 19 biles with crystals but only in three (15.7 ± 2.4% of total cholesterol) of 14 biles without crystals. There was no relation between biliary lipid concentration or the cholesterol saturation index and the percentage of vesicular cholesterol in biles with or without crystals. The close association of vesicles and crystals in human gallbladder bile supports the contention that vesicles are important in the initial nucleation of cholesterol monohydrate crystals

The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri

In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (\u3e 97%) in comparison to the pure SCE (~ 42%), or the physical mixture (~ 47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (\u3e 90%), compared to the pure SBE (~ 21%), or the physical mixture (~ 24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Studies on hepatotoxicity induced by chlorinated hydrocarbons. II. Lipid metabolism and absorption spectrum of microsomal lipid in the mice exposed to 1, 1, 2, 2-tetrachloroethane

Female Cb mice weighing 20-23 g were exposed to 800 ppm (in average) of 1, I, 2, 2.tetrachloroethane for 3 hours. Both triglyceride and phospholipid in the liver and plasma were determined at varying times after the exposure. On the other hand, there were observed the ultraviolet absorption spectra of microwmallipids in the liver at 90 minutes after the 1, 1,2, 2-tetrachloroethane or the carbon tetrachloride exposure. The results thus obtained are summarized as follows: 1. The increase of hepatic triglyceride contents attained the maximum level in the period between 20 and 25 hours after the exposure and declined to the initial levels at 90 hours later. 2. The plasma triglyceride levels decreased until 25 hours after the exposure, then tended to increase significantly and were much higher than the control levels in the period between 70 and 90 hours later. 3. Both liver and plasma phospholipid levels decreased gradually up to 25 hours after the exposure, then slowly recovered with almost the same rate of increase. 4. It was suggested that the inhalation of the above vapors induced a little change in microsomal lipids in the liver.</p

Substrate-Specific Inhibition Constants for Phospholipase A2 Acting on Unique Phospholipid Substrates in Mixed Micelles and Membranes Using Lipidomics.

Assaying lipolytic enzymes is extremely challenging because they act on water-insoluble lipid substrates, which are normally components of micelles, vesicles, and cellular membranes. We extended a new lipidomics-based liquid chromatographic-mass spectrometric assay for phospholipases A2 to perform inhibition analysis using a variety of commercially available synthetic and natural phospholipids as substrates. Potent and selective inhibitors of three recombinant human enzymes, including cytosolic, calcium-independent, and secreted phospholipases A2 were used to establish and validate this assay. This is a novel use of dose-response curves with a mixture of phospholipid substrates, not previously feasible using traditional radioactive assays. The new application of lipidomics to developing assays for lipolytic enzymes revolutionizes in vitro testing for the discovery of potent and selective inhibitors using mixtures of membranelike substrates

Souvenaid in the Management of Mild Cognitive Impairment: An Expert Consensus Opinion

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. Methods An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Summary of opinion Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer’s disease (AD), including those with MCI due to AD (prodromal AD). Conclusion Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a multimodal management approach including lifestyle risk factor modification and consideration of the multinutrient Souvenaid