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

Trends in prodrug research

An oral drug delivery system which comprises a biliquid foam comprising: from 1 to 20% by weight of a continuous hydrophilic phase, from 70 to 98% by weight of a pharmaceutically acceptable oil which forms a discontinuous phase, the said pharmaceutically acceptable oil having dissolved or dispersed therein a poorly water-soluble drug in an amount of from 0.1 to 20% by weight and the biliquid foam including therein from 0.5 to 10% by weight of a surfactant to enable the formation of a stable biliquid foam, all percentages being based upon the total weight of the formulation.

Oral delivery system comprising a biliquid foam

12,28-Oxamanzamine A (1), 12,28-oxa-8-hydroxymanzamine A (2), and 31-keto-12,34-oxa-32,33-dihydroircinal A (3) were isolated from two collections of an Indo-Pacific sponge, and their structures were assigned on the basis of 1D and 2D NMR spectroscopic data. These compounds possess a novel manzamine-type ring system generated through a new ether bridge formed between carbons 12 and 28 or between carbons 12 and 34 of the typical manzamine structure and add to our growing understanding of manzamine SAR and metabolism. Based on molecular modeling studies, the formation of these oxidation products is highly sterically favored. The potent antiinflammatory, antifungal, and anti-HIV-1 activity for a number of previously reported manzamines is also presented in addition to the pharmacokinetic studies of manzamine A (5). Oral and intravenous pharmacokinetic studies of manzamine A in rats indicated the compound to have low metabolic clearance, a reasonably long pharmacokinetic half-life, and good absolute oral bioavailability of 20.6%, which supports the value of these compounds as potential leads for further preclinical assessment and possible development.

New Manzamine Alkaloids from an Indo-Pacific Sponge. Pharmacokinetics, Oral Availability, and the Significant Activity of Several Manzamines Against HIV-I, AIDS Opportunistic Infections, and Inflammatory Diseases.

Presystemic acetylation of platelet cyclooxygenase: Selective inhibition by controlled release-low dose aspirin

Sir, We read with interest a recent article by Taguchi and co-workers (1) which described a chronically catheterized rabbit model for epidural administration. We have considerable experience with a rabbit model using a direct injection technique (2,3), and wish to bring to the attention of the article's readership two points which may be of interest. Firstly, chronic epidural catheterization has inherent problems such as infection, tissue reaction, catheter migration and possible dislodgment, which are significant complications when using a small animal model. Consequently, the experimental design using a chronically catheterized animal must allow for, and is constrained by, the need to confirm the position and patency of the catheter prior to experimentation. Direct epidural injection utilising a short bevel needle and a modified loss-of-resistance technique avoids these catheter-related problems (Z), and this may be a more appropriate approach especially if there is a long interval between injections. Our previously described epidural technique in the rabbit (2, 3) is simple, straightforward, easy to learn and is consistently reproducible. Our experience now exceeds in excess of 300 injections with a stable success rate of at least 85%. Secondly, we have recently identified some limitations with the use of the epidural rabbit model when attempting to 'scale' drug/drug formulation data to higher animal species (4). For example, absorption of lidocaine after epidural administration in the rabbit model was a rapid process adequately characterised by a single absorption phase, whereas absorption after epidural administration in the dog was a slower biphasic process (3,4). It appeared that differences in epidural absorption kinetics between the rabbit and dog may have been responsible for the differential pharmacodynamic effects observed with a slow-release lidocaine formulation in these two species. These observations highlight the need to consider carefully the absorption and pharmacokinetic characteristics of animal models chosen to evaluate epidural drug administration. F! J. Hughes W. N. Charman

William N. Charman

Papers

Trends in prodrug research

Oral delivery system comprising a biliquid foam

New Manzamine Alkaloids from an Indo-Pacific Sponge. Pharmacokinetics, Oral Availability, and the Significant Activity of Several Manzamines Against HIV-I, AIDS Opportunistic Infections, and Inflammatory Diseases.

Presystemic acetylation of platelet cyclooxygenase: Selective inhibition by controlled release-low dose aspirin

Rabbit epidural model