Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils

Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case

Agricultural peatlands: towards a greenhouse gas sink - a synthesis of a Dutch landscape study

It is generally known that managed, drained peatlands act as carbon (C) sources. In this study we examined how mitigation through the reduction of the intensity of land management and through rewetting may affect the greenhouse gas (GHG) emission and the C balance of intensively managed, drained, agricultural peatlands. Carbon and GHG balances were determined for three peatlands in the western part of the Netherlands from 2005 to 2008 by considering spatial and temporal variability of emissions (CO2, CH4 and N2O). One area (Oukoop) is an intensively managed grass-on-peatland area, including a dairy farm, with the ground water level at an average annual depth of 0.55 (±0.37) m below the soil surface. The second area (Stein) is an extensively managed grass-on-peatland area, formerly intensively managed, with a dynamic ground water level at an average annual depth of 0.45 (±0.35) m below the soil surface. The third area is a (since 1998) rewetted former agricultural peatland (Horstermeer), close to Oukoop and Stein, with the average annual ground water level at a depth of 0.2 (±0.20) m below the soil surface. During the measurement campaigns we found that both agriculturally managed sites acted as C and GHG sources and the rewetted former agricultural peatland acted as a C and GHG sink. The ecosystem (fields and ditches) total GHG balance, including CO2, CH4 and N2O, amounted to 3.9 (±0.4), 1.3 (±0.5) and -1.7 (±1.8) g CO2-eq m-2 d-1 for Oukoop, Stein and Horstermeer, respectively. Adding the farm-based emissions to Oukoop and Stein resulted in a total GHG emission of 8.3 (±1.0) and 6.6 (±1.3) g CO2-eq m-2 d-1, respectively. For Horstermeer the GHG balance remained the same since no farm-based emissions exist. Considering the C balance (uncertainty range 40–60%), the total C release in Oukoop and Stein is 5270 and 6258 kg C ha-1 yr-1, respectively (including ecosystem and management fluxes), and the total C uptake in Horstermeer is 3538 kg C ha-1 yr-1. Water bodies contributed significantly to the terrestrial GHG balance because of a high release of CH4. Overall, this study suggests that managed peatlands are large sources of GHGs and C, but, if appropriate measures are taken, they can be turned back into GHG and C sinks within 15 years of abandonment and rewetting. The shift from an intensively managed grass-on-peat area (Oukoop) to an extensively managed one (Stein) reduced the GHG emissions mainly because N2O emission and farm-based CH4 emissions decreased

Ferulic acid and derivatives: molecules with potential application in the pharmaceutical field

Ferulic acid is a phenolic acid widely distributed in the plant kingdom. It presents a wide range of potential therapeutic effects useful in the treatments of cancer, diabetes, lung and cardiovascular diseases, as well as hepatic, neuro and photoprotective effects and antimicrobial and anti-inflammatory activities. Overall, the pharmaceutical potential of ferulic acid can be attributed to its ability to scavenge free radicals. However, recent studies have revealed that ferulic acid presents pharmacological properties beyond those related to its antioxidant activity, such as the ability to competitively inhibit HMG-CoA reductase and activate glucokinase, contributing to reduce hypercholesterolemia and hyperglycemia, respectively. The present review addresses ferulic acid dietary sources, the pharmacokinetic profile, antioxidant action mechanisms and therapeutic effects in the treatment and prevention of various diseases, in order to provide a basis for understanding its mechanisms of action as well as its pharmaceutical potential

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Regulation of phytosterol and phytoalexin biosynthesis in plant tissue cultures

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN002412 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Fluorescence study of the motional states of core and surface lipids in native and reconstituted low density lipoproteins

Low density lipoproteins (LDL) consist of an apolar core of cholesterol esters and triglycerides surrounded by a monolayer of phospholipid, cholesterol, and a single molecule of apolipoprotein B (apoB-100). To determine the influence of core and surface constituents on the surface order of LDL, we have measured core and surface order parameters for native LDL, and reconstituted LDLs (rLDL) whose apolar core lipids were extracted and replaced with either cholesterol oleate (CO) or triolein (TO). Order parameters were measured by fluorescence depolarization of diphenylhexatriene (DPH), which is located primarily in the core, and of trimethylammoniumdiphenylhexatriene (TMA-DPH), which is anchored at the waterphospholipid interface. DPH order parameters for LDL reconstituted with TO (r-[TO] LDL) were much lower than those for LDL reconstituted with CO (r-[CO]LDL), consistent with the physical properties of TO, a nonviscous liquid at all temperatures studied, and CO, which exists in a liquid crystalline or viscous liquid state at the temperatures studied. Although core cholesterol esters in r[CO]LDL and native LDL undergo distinct order-disorder transitions, these transitions were not detected by DPH. This is most likely due to the difference between the time scale for end-over-end tumbling of cholesterol esters and the fluorescence lifetime of DPH. Despite the fact that the core lipids of r-[CO]LDL were much more ordered than those of r- [TO] LDL, surface order parameters for both lipoproteins were similar. We conclude that the motional states of the core and surface lipids are relatively independent. Surface order parameters for native LDL were higher than those for reconstituted LDLs. This was attributed to the presence of unesterified cholesterol in the surface of native LDL, and its absence in reconstituted LDL. Finally, the outer surface of r-[CO]LDL was shown to be more ordered than that of unilamellar vesicles. We suggest that this is due to the presence of apoB-100 and neutral lipid molecules in the highly curved surface of LDL which reduce the motional freedom of surface phospholipids

Convergence of Brillouin zone summations

A simple method to overcome convergence problems in Brillouin zone summations of lattice dynamical properties is proposed, which makes use of evenly spread sample points and gives a special treatment to points close to the Brillouin zone origin

Hoisting a red flag: An early warning system for exceeding subsidence limits

We present a general framework that enables decision-making when a threshold in a process is about to be exceeded (an event). Measurements are combined with prior information to update the probability of such an event. This prior information is derived from the results of an ensemble of model realisations that span the uncertainty present in the model before any measurements are collected; only probability updates need to be calculated, which makes the procedure very fast once the basic ensemble of realisations has been set up. The procedure is demonstrated with an example where gas field production is restricted to a maximum amount of subsidence. Starting with 100 realisations spanning the prior uncertainty of the process, the measurements collected during monitoring bolster some of the realisations and expose others as irrelevant. In this procedure, more data will mean a sharper determination of the posterior probability. We show the use of two different types of limits, a maximum allowed value of subsidence and a maximum allowed value of subsidence rate for all measurement points at all times. These limits have been applied in real world cases. The framework is general and is able to deal with other types of limits in just the same way. It can also be used to optimise monitoring strategies by assessing the effect of the number, position and timing of the measurement points. Furthermore, in such a synthetic study, the prior realisations do not need to be updated; spanning the range of uncertainty with appropriate prior models is sufficient. © International Association for Mathematical Geosciences 2009

[Cranio-maxillofacial traumatology]

Item does not contain fulltextDuring the last 50 years, significant developments have taken place in the treatment of cranio-maxillofacial fractures. The aim of treatment is to achieve the most complete possible restoration of facial functions Epidemiologic figures for these fractures are sparsely available in the literature, but traffic accidents, acts of violence and sports injuries appear to be the main causes. Currently, treatment of facial trauma is aimed at early and (nearly) complete restoration of function. To achieve this goal almost exclusive use is made of stable osteosynthesis methods in The Netherlands. An optimal fixation method exists for nearly every cranio-maxillofacial trauma due to the availability of a large variety of osteosynthesis materials, from micro-plates to reconstruction plates