Effect of preduodenal lipase inhibition in suckling rats on dietary octanoic acid (C8:0) gastric absorption and plasma octanoylated ghrelin concentration.

Part of medium chain fatty acids (MCFAs) coming from dietary triglycerides (TGs) can be directly absorbed through the gastric mucosa after the action of preduodenal lipase (lingual lipase in the rat). MCFA gastric absorption, particularly that of octanoic acid (C8:0), may have a physiological importance in the octanoylation of ghrelin, the orexigenic gastric peptide acting as an endogenous ligand of the hypothalamic growth hormone secretagogue receptor 1a (GHSR-1a). However, the amount of C8:0 absorbed in the stomach and its metabolic fate still haven't been clearly characterized. The purpose of the present study was to further characterize and quantify the importance of preduodenal lipase activity on the release and gastric absorption of dietary C8:0 and on the subsequent ghrelin octanoylation in the stomach mucosa. Fifteen days old rats received fat emulsions containing triolein or [1,1,1-(13)C]-Tri-C8:0 and a specific inhibitor of preduodenal lipase, 5-(2-(benzyloxy)ethoxy)-3-(3-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one or BemPPOX. The fate of the (13)C-C8:0 was followed in rat tissues after 30 and 120min of digestion and octanoylated ghrelin was measured in the plasma. This work (1) demonstrates that part of C8:0 coming from Tri-C8:0 is directly absorbed at the gastric level, (2) allows the estimation of C8:0 gastric absorption level (1.3% of the (13)C-C8:0 in sn-3 position after 30min of digestion), as well as (3) the contribution of rat lingual lipase to total lipolysis and to duodenal absorption of dietary FAs (at least 30%), (4) shows no short-term effect of dietary Tri-C8:0 consumption and subsequent increase of C8:0 gastric tissue content on plasma octanoylated ghrelin concentration.

Novel concept suppressing plasma heat pulses in a tokamak by fast divertor sweeping.

One of the remaining challenges in magnetic thermonuclear fusion is survival of the heat shield protecting the tokamak reactor vessel against excessive plasma heat fluxes. Unmitigated high confinement edge localized mode (ELM) is a regular heat pulse damaging the heat shield. We suggest a novel concept of magnetic sweeping of the plasma contact strike point fast and far enough in order to spread this heat pulse. We demonstrate feasibility of a dedicated copper coil in a resonant circuit, including the induced currents and power electronics. We predict the DEMO ELM properties, simulate heat conduction, 3D particles motion and magnetic fields of the plasma and coil in COMSOL Multiphysics and Matlab. The dominant system parameter is voltage, feasible 18 kV yields 1 kHz sweeping frequency, suppressing the ELM-induced surface temperature rise by a factor of 3. Multiplied by other known mitigation concepts, ELMs might be mitigated enough to ensure safe operation of DEMO.

Studying Gastric Lipase Adsorption Onto Phospholipid Monolayers by Surface Tensiometry, Ellipsometry, and Atomic Force Microscopy.

The access to kinetic parameters of lipolytic enzyme adsorption onto lipids is essential for a better understanding of the overall catalytic process carried out by these interfacial enzymes. Gastric lipase, for instance, shows an apparent optimum activity on triglycerides (TAG) at acidic pH, which is controlled by its pH-dependent adsorption at lipid-water interfaces. Since gastric lipase acts on TAG droplets covered by phospholipids, but does not hydrolyze these lipids, phospholipid monolayers spread at the air-water interfaces can be used as biomimetic interfaces to study lipase adsorption and penetration through the phospholipid layer, independently from the catalytic activity. The adsorption of recombinant dog gastric lipase (rDGL) onto 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) monolayers can be monitored by surface tensiometry at various enzyme concentrations, pHs, and surface pressures (Π). These experimental data and the use of Langmuir adsorption isotherm and Verger-de Haas' lipase kinetics models further allow estimating various parameters including the adsorption equilibrium constant (KAds), the interfacial concentration [Formula: see text] , the molar fraction [Formula: see text] (ΦE*(%), mol%), and the molecular area [Formula: see text] of rDGL adsorbed onto the DLPC monolayer under various conditions. Additional insight into rDGL adsorption/insertion on phospholipid monolayers can be obtained by combining ellipsometry, Langmuir-Blodgett film transfer, and atomic force microscopy. When using multicomponent phospholipid monolayers with phase separation, these techniques allow to visualizing how rDGL preferentially partitions toward liquid expanded phase and at phase boundaries, gets adsorbed at various levels of insertion and impacts on the lateral organization of lipids.

Inhibition of human gastric and pancreatic lipases by chiral alkylphosphonates. A kinetic study with 1,2-didecanoyl-sn-glycerol monolayer.

Enantiomerically pure alkylphosphonate compounds RR'P(O)PNP (R = CnH2n + 1, R' = OY with Y = Cn'H2n' + 1 with n = n' or n not equal to n'; PNP = p-nitrophenoxy) noted (RY), mimicking the transition state occurring during the carboxyester hydrolysis were synthesized and investigated as potential inhibitors of human gastric lipase (HGL) and human pancreatic lipase (HPL). The inhibitory properties of each enantiomer have been tested with the monomolecular films technique in addition to an enyzme linked immunosorbent assay (ELISA) in order to estimate simultaneously the residual enzymatic activity as well as the interfacial lipase binding. With both lipases, no obvious correlation between the inhibitor molar fraction (alpha 50) leading to half inhibition, and the chain length, R or Y was observed. (R11Y16)s were the best inhibitor of HPL and (R10Y11)s were the best inhibitors of HGL. We observed a highly enantioselective discrimination, both with the pure enantiomeric alkylphosphonate inhibitors as well as a scalemic mixture. We also showed, for the first time, that this enantioselective recognition can occur either during the catalytic step or during the initial interfacial adsorption step of the lipases. These experimental results were analyzed with two kinetic models of covalent as well as pseudo-competitive inhibition of lipolytic enzymes by two enantiomeric inhibitors.

Note: On the measurement of plasma potential fluctuations using emissive probes.

In this Note, it is pointed out that emissive probes cannot be used to directly and reliably measure plasma potential fluctuations. An experimentally validated model demonstrates indeed that the floating potential fluctuations of an emissive probe which floats at the mean plasma potential depend not only on the plasma potential fluctuations but also on electron density and temperature fluctuations.

Design and validation of the ball-pen probe for measurements in a low-temperature magnetized plasma.

Ball-pen probes have been used in fusion devices for direct measurements of the plasma potential. Their application in low-temperature magnetized plasma devices is still subject to studies. In this context, a ball-pen probe has been recently implemented on the linear plasma device Mirabelle. Produced by a thermionic discharge, the plasma is characterized by a low electron temperature and a low density. Plasma confinement is provided by an axial magnetic field that goes up to 100 mT. The principle of the ball-pen probe is to adjust the saturation current ratio to 1 by reducing the electron current contribution. In that case, the floating potential of the probe is close to the plasma potential. A thorough study of the ball-pen probe operation is performed for different designs of the probe over a large set of plasma conditions. Comparisons between ball-pen, Langmuir, and emissive probes are conducted in the same plasma conditions. The ball-pen probe is successfully measuring the plasma potential in these specific plasma conditions only if an adapted electronics and an adapted probe size to the plasma characteristic lengths (λ(D), ρ(ce)) are used.

Discrimination between closed and open forms of lipases using electrophoretic techniques.

The enhanced catalytic activity of lipases is often associated with structural changes. The three-dimensional (3D) structures showed that the covalently inhibited lipases exist under their open conformations, in contrast to their native closed forms. We studied the inhibition of various lipases--human and dog gastric lipases, human pancreatic lipase, and Humicola lanuginosa lipase--by the octyl-undecyl phosphonate inhibitor, and we measured the subsequent modifications of their respective electrophoretic mobility. Furthermore, the experimental values of the isoelectric points found for the native (closed) and inhibited (open) lipases are in agreement with theoretical calculations based on the electrostatic potential. We concluded that there is a significant difference in the isoelectric points between the closed (native) and open (inhibited) conformations of the four lipases investigated. Thus, analysis of the electrophoretic pattern is proposed as an easy experimental tool to differentiate between a closed and an open form of a given lipase.

Covalent inhibition of digestive lipases by chiral phosphonates.

Designing and synthesizing specific inhibitors is of fundamental value for understanding the molecular mechanisms involved in the interfacial adsorption step as well as the catalytic activity of lipases. In this Account, we will review and discuss results obtained mostly at our laboratory concerning the covalent inhibition of human gastric and human pancreatic lipases by chiral phosphonates. Rather than presenting an exhaustive list of compounds tested so far with lipases of animal and microbial origin, we selected recent experimental data illustrating well the specific problems encountered during the covalent inhibition of these digestive lipases.

[Adaptation of a freezing technic with a low concentration of glycerol for preserving red blood cells resuspended in saline-adenine-glucose]. / Adaptation de la technique de congélation avec faible concentration en glycérol à des concentrés globulaires resuspendus en SAG.

We describe here a freezing method with a final low concentration of 20% glycerol and storage in a aluminium flask at - 150 degrees C. This technique allows the freezing of red blood cells concentrates collected on CPD and resuspended in SAG, without having to eliminate the SAG solution. For this we used an initial solution of 60% glycerol, which we added to the red blood cell concentrate in two steps separated by a resting time. Accordingly to the final concentration of glycerol, this freezing process is similar to the method currently used in our laboratory. This consists in one step addition V/V of 40% glycerol solution to the CPD red blood cells. The two techniques have been compared after thawing, and washing in a IBM Blood Processor 2991. The following parameters have been studied mainly: --haemoglobin level --residual glycerol --leucocytes and platelets --amount of 2-3 DPG and of intra-erythrocyte ATP. The results of the two freezing techniques are similar. They show that the SAG solution does not impair the intracellular penetration of glycerol. The in vitro qualities of the erythrocytes are well preserved.

Modification of the vermont test for monitoring fat adulteration of dairy products.

The Vermont test was developed for the routine screening of dairy products for vegetable fat adulteration. A slight modification of the test procedure made it more rapid and reduced costs. Gas-liquid chromatographic analysis of saponified fatty acids in the first and second Mojonnier extractions were proportional; thus, only the first extraction was needed to determine the purity of a milk lipid sample. This modification saves about 8 min/series of four samples and conserves 48% of the volume of organic solvents necessary to perform the classical Mojonnier extraction.

Neuropsychiatric side effects related to treatment with felbamate.

Seven patients with refractory seizure disorders and neuropsychiatric symptoms believed secondary to felbamate are presented. Five were on concomitant valproic acid (and other agents). Anergia, apathy, bradyphrenia, and increased irritability were prominent. One patient on felbamate monotherapy had a new-onset psychosis. Felbamate's NMDA receptor antagonism and GABA potentiation (perhaps enhanced by valproic acid use) are discussed as possible mechanisms of these side effects.

Catechol derivatives of aminopyrazine and cell protection against UVB-induced mortality.

A series of 5-aryl- and 3,5-bis-aryl-2-amino-1,4-pyrazine derivatives 4 and 6, and related imidazolopyrazinones 7, has been synthesized, the aryl groups of which are catechol and/or phenol substituents. These compounds, tested against human keratinocyte cells stressed by UVB irradiation, showed high antioxidative properties. One compound (6f) was more active than EGCG/ECG (green tea extract) in reducing cell mortality.

Perception of orthodontic treatment need: opinion comparisons of orthodontists, pediatric dentists, and general practitioners.

AIM: To determine the relationship between treatment need assessment scores of orthodontists, general practitioners, and pediatric dentists. STUDY DESIGN: Observational. SAMPLE: Ten general dental practitioners, 18 orthodontists and 15 pediatric dentists reviewed 137 dental casts and recorded their opinion on whether orthodontic treatment was needed. RESULTS: We found a high level of agreement between pediatric dentists, orthodontists and general practitioners (Kappa range 0.86-0.95). Between the groups, the amount of agreement was lower. CONCLUSIONS: Orthodontists, general dental practitioners, and pediatric dentists in this sample exhibit high levels of agreement on orthodontic treatment need.