https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

/pdf/a-standardised-static-in-vitro-digestion-method-suitable-for-tvm9kgy0s3.pdf

A standardised static in vitro digestion method suitable for food – an international consensus

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.

/pdf/new-substructure-filters-for-removal-of-pan-assay-3e3dudtvn0.pdf

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase isoenzymes, and their biosynthesis is blocked by nonsteroidal antiinflammatory drugs, including those selective for inhibition of cyclooxygenase-2. Despite the clinical efficacy of nonsteroidal antiinflammatory drugs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm.

Prostaglandins and Inflammation

High throughput, quantitative analysis of human osteoclast differentiation and activity.

Influence of physicochemical properties on the patterns of association of a series of aliphatic esters of halofantrine with plasma lipoproteins.

Purpose. Phase II metabolism involves the conjugation of a polar moiety, such as sulfate or glucuronic acid, to a (relatively) nonpolar xenobiotic. Although it might be expected that such conjugates may exhibit amphiphilic character (e.g., surface activity and potential to form micelles), no detailed study of the micellization characteristics of any drug-glucuronide conjugates has yet been reported. Therefore, the aim of this study was to investigate the solution behavior and amphiphilic characteristics of gemfibrozil 1-O-β glucuronide (GG), a model drug-glucuronide conjugate.

Self-micellization of gemfibrozil 1-O-β acyl glucuronide in aqueous solution

Elevated systemic levels of triglyceride-rich lipoproteins (TRL) are a risk factor for the development of atherosclerosis. In patients with metabolic syndrome (MetS), intestinal TRL overproduction contributes to high systemic TRL levels, and recent studies suggest that systemic changes in MetS such as increases in plasma fatty acids and insulin resistance stimulate intestinal TRL production. The current study has examined whether increases in systemic TRL influence intestinal lipid transport and lipoprotein assembly pathways and evaluates the impact of these changes on the absorption and lymphatic transport of lipids and a model lipophilic drug (halofantrine). Mesenteric lymph-duct or bile-duct cannulated rats were administered IV saline or (14)C-labeled chylomicron (CM) (to increase systemic TRL) and intraduodenal (3)H lipids and drug. Changes to biliary lipid output and lymphatic lipid and drug transport were subsequently examined. Increasing systemic TRL concentrations stimulated a significant increase in lymphatic lipid and drug transport. The increased lipids in lymph were not derived from bile or the intestinal blood supply (fatty acid or IV infused (14)C-CM). Rather, an increase in lymphatic transport of duodenally sourced lipids was evident. Increasing plasma levels of TRL therefore stimulated lipid absorption and lymphatic transport via a positive feedback process. The data also suggest that the changes to intestinal TRL formation that result from raised systemic TRL levels may impact on the absorption of highly lipophilic drugs and therefore the reproducibility of drug treatments.

William N. Charman

Papers

High throughput, quantitative analysis of human osteoclast differentiation and activity.

Influence of physicochemical properties on the patterns of association of a series of aliphatic esters of halofantrine with plasma lipoproteins.

Self-micellization of gemfibrozil 1-O-β acyl glucuronide in aqueous solution

Acute Hypertriglyceridemia Promotes Intestinal Lymphatic Lipid and Drug Transport: A Positive Feedback Mechanism in Lipid and Drug Absorption

Differences in pre- and post-prandial plasma lipid profiles affect the extraction efficiency of a model highly lipophilic drug from beagle dog plasma.