Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis

Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75432/1/j.1365-2222.2006.02498.x.pd

Cell signalling by reactive lipid species: new concepts and molecular mechanisms

The process of lipid peroxidation is widespread in biology and is mediated through both enzymatic and non-enzymatic pathways. A significant proportion of the oxidized lipid products are electrophilic in nature, the RLS (reactive lipid species), and react with cellular nucleophiles such as the amino acids cysteine, lysine and histidine. Cell signalling by electrophiles appears to be limited to the modification of cysteine residues in proteins, whereas non-specific toxic effects involve modification of other nucleophiles. RLS have been found to participate in several physiological pathways including resolution of inflammation, cell death and induction of cellular antioxidants through the modification of specific signalling proteins. The covalent modification of proteins endows some unique features to this signalling mechanism which we have termed the ‘covalent advantage’. For example, covalent modification of signalling proteins allows for the accumulation of a signal over time. The activation of cell signalling pathways by electrophiles is hierarchical and depends on a complex interaction of factors such as the intrinsic chemical reactivity of the electrophile, the intracellular domain to which it is exposed and steric factors. This introduces the concept of electrophilic signalling domains in which the production of the lipid electrophile is in close proximity to the thiol-containing signalling protein. In addition, we propose that the role of glutathione and associated enzymes is to insulate the signalling domain from uncontrolled electrophilic stress. The persistence of the signal is in turn regulated by the proteasomal pathway which may itself be subject to redox regulation by RLS. Cell death mediated by RLS is associated with bioenergetic dysfunction, and the damaged proteins are probably removed by the lysosome-autophagy pathway

Assessment of potential risks of chemicals and plastic particles from offshore wind turbines

Windenergie is belangrijk om de overgang van fossiele naar duurzame energie mogelijk te maken. Daarom zullen er in de toekomst onder andere veel meer windturbines op zee komen. Zogeheten epoxy coatings en ‘opofferingsmetalen’ kunnen worden gebruikt om windturbines te beschermen tegen corrosie. Uit deze materialen kunnen chemische stoffen vrijkomen. Het RIVM heeft uitgezocht of dit schadelijk kan zijn voor mens en milieu. Daarnaast is een inschatting gemaakt hoeveel plastic deeltjes vrijkomen door slijtage van de turbinebladen. Op dit moment is niet bekend of bij Nederlandse windturbines op zee daadwerkelijk epoxy coatings en opofferingsmetalen worden gebruikt. Het RIVM heeft daarom een denkbeeldig scenario doorgerekend om inzicht te krijgen in mogelijke schadelijke effecten áls ze worden gebruikt. Om deze effecten niet te onderschatten heeft het RIVM gerekend met de ongunstigste aannames over de hoeveelheid stoffen die vrijkomen. Zeker is dat de uitstoot van zink, indium, lood en cadmium uit opofferingsmetalen bij windturbines op zee niet schadelijk zijn voor mens en milieu. Het gebruik van epoxy coatings kan mogelijk wel schadelijk zijn. Of dit in de praktijk ook echt zo is, hangt sterk af van de gebruikte coating. Het verschilt namelijk per coating hoeveel en welke stoffen er uit kunnen vrijkomen. Het is daarom belangrijk om een beter beeld te krijgen welke coatings bij de huidige windturbines op zee worden gebruikt. Ook beveelt het RIVM aan om bij nieuwe windturbines uit voorzorg coatings te gebruiken waar geen of weinig stoffen uit weglekken. Er is nog weinig informatie beschikbaar over hoeveel plastic deeltjes door slijtage van turbinebladen in de omgeving terechtkomen. Het RIVM schat dat de hoeveelheid plastic deeltjes die hierdoor in de zee komt kleiner is dan via andere bronnen, zoals de Nederlandse scheepvaart. Er bestaan tegenwoordig technieken om die slijtage zo veel mogelijk tegen te gaan. De precieze hoeveelheid deeltjes hangt onder andere sterk af van de gebruikte techniek. Dit onderzoek is uitgevoerd in opdracht van het Staatstoezicht op de Mijnen (SodM). Het is een vervolg op een quickscan uit 2022 waarin verschillende aandachtspunten zijn benoemd. Zie ook de publicatie: Inzicht in emissies van chemische stoffen bij windturbines op zee (gepubliceerd op 13-06-2022)Wind energy is important to facilitate the transition from fossil fuels to sustainable energy. For this reason, many more offshore wind turbines will be installed in the future. Epoxy coatings and ‘sacrificial metals’ can be used to protect wind turbines against corrosion. These materials may release chemicals. RIVM has investigated whether this could be harmful to human health and the environment. It has also made an estimate of the amount of plastic particles released due to wear and tear of the turbine blades. At present, it is unknown whether epoxy coatings and sacrificial metals are actually used in Dutch offshore wind turbines. RIVM therefore used a hypothetical scenario to gain insight into the potential harmful effects if these materials are indeed used. To avoid underestimating these effects, RIVM based its calculations on the most unfavourable assumptions about the amount of substances released. What is certain is that the release of zinc, indium, lead and cadmium from sacrificial metals on offshore wind turbines is not harmful to human health and the environment. However, the use of epoxy coatings may be harmful. Whether this is actually the case in practice depends largely on the coating used, as the amounts and types of substances that may be released vary from one coating to the next. It is therefore important to obtain a clearer picture of which coatings were used on existing offshore wind turbines. As a precaution, RIVM also recommends using coatings on new wind turbines that cause little to no release of substances. Little information is available about how many plastic particles end up in the environment due to wear and tear of turbine blades. RIVM estimates that the amount of plastic particles that end up in the sea this way is lower than from other sources, such as the Dutch shipping industry. Modern techniques minimise this wear and tear. The precise amount of particles released is highly dependent on factors such as the technique used. This study was commissioned by the Dutch State Supervision of Mines (SodM). It is a follow-up to a quick scan from 2022 in which various points for attention were identified

Loosely coupling web-applications

When developers of two web-based environments wish to share activities, they need to negotiate the ways to do so. It may boil down to an a simple authorization, or URL exchange. Generally, however, the exchange is more convoluted and measures have to be taken to guarantee the highest quality in the browsing experience. We address this problem in an attempt to generalize the action of following a hyperlink into a browser delegation. Report on the experience gained in implementing the delegation between ACTIVEMATH and SIETTE is provided

Loosely coupling web-applications

When developers of two web-based environments wish to share activities, they need to negotiate the ways to do so. It may boil down to an a simple authorization, or URL exchange. Generally, however, the exchange is more convoluted and measures have to be taken to guarantee the highest quality in the browsing experience. We address this problem in an attempt to generalize the action of following a hyperlink into a browser delegation. Report on the experience gained in implementing the delegation between ACTIVEMATH and SIETTE is provided

Interactive learning and mathematical calculus

A variety of problems in mathematical calculus can be solved by recursively applying a ??nite number of rules. Often, a generic solving strategy can be extracted and an interactive exercise system that emulates a tutor can be implemented. In this paper we show how software developed by us can be used to realize this interactivity. In particular, an implementation of a generic exercise for computing the derivative of elementary functions is presented

Interactive learning and mathematical calculus

Abstract. A variety of problems in mathematical calculus can be solved by recursively applying a finite number of rules. Often, a generic solving strategy can be extracted and an interactive exercise system that emulates a tutor can be implemented. In this paper we show how software developed by us can be used to realize this interactivity. In particular, an implementation of a generic exercise for computing the derivative of elementary functions is presented.