Realization of an advanced super-mirror solid-state neutron polarizer for the instrument PF1B at the Institut Laue-Langevin.

In this last of a series of three papers on the development of an advanced solid-state neutron polarizer, we present the final construction of the polarizer and the results of its commissioning. The polarizer uses spin-selective reflection of neutrons by interfaces coated with polarizing super-mirrors. The polarizer is built entirely in-house for the PF1B cold neutron beam facility at the Institut Max von Laue-Paul Langevin (ILL). It has been installed in the PF1B casemate and tested under real conditions. The average transmission for the "good" spin component is measured to be >30%. The polarization averaged over the capture spectrum reaches a record value of Pn ≈ 0.997 for the full angular divergence in the neutron beam, delivered by the H113 neutron guide, and the full wavelength band λ of 0.3-2.0 nm. This unprecedented performance is due to a series of innovations in the design and fabrication in the following domains: choice of the substrate material, super-mirror and anti-reflecting multilayer coatings, magnetizing field, and assembling process. The polarizer is used for user experiments at PF1B since the last reactor cycle in 2020.

A project of advanced solid-state neutron polarizer for PF1B instrument at Institut Laue-Langevin.

Among polarizers based on the neutron reflection from Super-Mirrors (SMs), solid-state neutron-optical devices have many advantages. The most relevant is the 5-10 times smaller size along the neutron beam direction compared to more traditional air-gap devices. An important condition for a good SM polarizer is the matching of the substrate SLD (Scattering Length Density) with the SM coating SLD for the spin-down component. For traditional Fe/Si SM on the Si substrate, this SLD step is positive when a neutron goes from the substrate to the SM, which leads to a significant degradation of the polarizer performance in the small Q region. This can be solved by replacing single-crystal Si substrates by single-crystal sapphire or quartz substrates. The latter shows a negative SLD step for the spin-down neutron polarization component at the interface with Fe and, therefore, avoid the total reflection regime in the small Q region. In order to optimize the polarizer performance, we formulate the concept of sapphire V-bender. We perform ray-tracing simulations of sapphire V-bender, compare results with those for traditional C-bender on Si, and study experimentally V-bender prototypes with different substrates. Our results show that the choice of substrate material, polarizer geometry, as well the strength and quality of magnetizing field have dramatic effect on the polarizer performance. In particular, we compare the performance of polarizer for the applied magnetic field strength of 50 mT and 300 mT. Only the large field strength (300 mT) provides an excellent agreement between the simulated and measured polarization values. For the double-reflection configuration, a record polarization >0.999 was obtained in the neutron wavelength band of 0.3-1.2 nm with only 1% decrease at 2 nm. Without any collimation, the polarization averaged over the full outgoing capture spectrum, 0.997, was found to be equal to the value obtained previously using only a double polarizer in the "crossed" (X-SM) geometry. These results are applied in a full-scale polarizer for the PF1B instrument.

Uniaxial pressure setup for piezoresistance and magnetoresistance measurements in Heusler materials.

We report on a new uniaxial pressure experimental setup for electrical resistivity measurements working in a 77 K-500 K temperature range and in a magnetic field up to 8 T. Such a continuous uniaxial pressure device enables the study of the piezoresistance and the pressure induced change in electrical properties of bulk samples. Strong influence of uniaxial pressure on transport properties is shown for Ni-Co-Mn-In Heusler single crystal material. A shift of the martensite-austenite first order transformation temperature is measured with an applied uniaxial pressure leading to an electrical resistance changed by up to 120%.

[Oral candidiasis and dentures]. / Candidoses orales et prothèses dentaires.

Yeasts belonging to the Candida genus usually colonize the human oral cavity. Immunocompromised patients or individuals with an imbalance of their oral microflora can develop yeast infections from this reservoir. However, saliva protects oral mucosa against candidosis; in turn, dry mouth is associated with increased yeast counts and candidosis risk. In vivo and in vitro studies have shown Candida incorporation into biofilms covering different biomaterials such as dentures: these biofilms may be an increased risk factor for invasive candidosis when the host immune system is compromised. Daily denture brushing is recommended to all wearers. Family or healthcare workers must take over this task when there is autonomy loss, especially in the elderly. In case of candidosis in denture wearers, decontamination of dentures is mandatory. Antimycotics (azoles, nystatin) must be kept for curative treatments of infected patients; they are less active against Candida biofilms on dentures and could lead to emergent resistance if applied daily to dentures against yeast colonization. There are several antiphlogistic solutions with antifungal properties. Nevertheless, literature data does not integrate all aspects of denture care: welfare of denture wearers, prevention of candidosis, biomaterial defects after decontamination processing, and taking into account possible Candida biofilm development. Daily brushing of dentures remains the key recommendation.

Identification of a tryptophan-like epitope borne by the variable surface glycoprotein (VSG) of African trypanosomes.

Antibodies (Ab) directed against a tryptophan-like epitope (WE) were previously detected in patients with human African trypanosomiasis (HAT). We investigated whether or not these Ab resulted from immunization against trypanosome antigen(s) expressing a WE. By Western blotting, we identified an antigen having an apparent molecular weight ranging from 60 to 65 kDa, recognized by purified rabbit anti-WE Ab. This antigen, present in trypomastigote forms, was absent in procyclic forms and Trypanosoma cruzi trypomastigotes. Using purified variable surface glycoproteins (VSG) from various trypanosomes, we showed that VSG was the parasite antigen recognized by these rabbit Ab. Anti-WE and anti-VSG Ab were purified from HAT sera by affinity chromatography. Immunoreactivity of purified antibodies eluted from affinity columns and of depleted fractions showed that WE was one of the epitopes borne by VSG. These data underline the existence of an invariant WE in the structure of VSG from several species of African trypanosomes.

Insulin-dependent diabetes and gut dysfunction: the BB rat model.

Accumulating data indicate that intestinal dysfunction and dysregulation of the gut immune system may play a role in the development of type 1 diabetes. This review deals with the occurrence of gut damage and dysfunction in BB rats, an animal model of spontaneous immune type 1 diabetes, placing special emphasis on the effect of diet on the incidence of diabetes in BB rats, the identification of a type 1 diabetes-related protein from wheat, and preliminary observations documenting anomalies in the inductive tissues of the gut immune system (Peyer's patch cells and mesenteric lymph node cells) and pancreatic lymph node cells of diabetes-prone BB rats. In addition to histological evidence of gut damage, the review will also draw attention to altered intestinal disaccharidase activity, changes in intestinal peroxidase activity, glucagon-like peptide 1 anomalies, and perturbation of both intestinal permeability and mucin content in BB rats. In all these cases, the findings in rats fed a diabetes-promoting diet are compared to those collected in animals receiving a protective diabetes-retardant diet.

Enteropathy precedes type 1 diabetes in the BB rat.

BACKGROUND AND AIMS: There is increasing evidence implicating intestinal immune responses to dietary proteins in the pathogenesis of type 1 autoimmune diabetes (T1D). Here we investigated the association between intestinal pathology and dietary factors in T1D by examining the mucosal architecture in the BB rat model. METHODS: BB control (BBc) and diabetes prone (BBdp) rats were fed either a diabetes retardant hydrolysed casein based diet or one of two cereal based diets that promote the development of diabetes. Intestinal architecture was assessed in the jejunum by microdissection, histology, and immunohistology, and by measuring peroxidase activity and brush border invertase levels. RESULTS: Enteropathy was present in BBdp rats soon after weaning, as assessed by increases in crypt length and in the proliferative activity of crypt epithelial cells in the jejunum, and this remained constant until 120 days of age. There was also a decrease in invertase activity, as well as increased numbers of intraepithelial lymphocytes, increased levels of mucosal peroxidase activity, and infiltration of the mucosa by CD4(+) T lymphocytes. Equivalent enteropathy was present at all times in BBdp rats and was not influenced by the nature of the diet or by thymectomy at three weeks at age, procedures which prevent the development of diabetes. CONCLUSION: Enteropathy is a consistent feature in the diabetes prone BB rat but it precedes the onset of insulitis and appears to be due to mechanisms distinct from those which cause diabetes. The beneficial effects of the diabetes retardant hydrolysed casein diet on diabetes are not due to an effect on intestinal architecture per se but mucosal damage may be necessary for the development of autoreactivity in the pancreas.

Enzyme-to-enzyme channelling in the early steps of glycolysis in rat pancreatic islets.

The metabolism of D-glucose displays anomeric specificity in rat pancreatic islets. The aim of the present report is to investigate whether such a situation implies enzyme-to-enzyme tunnelling of metabolites in the early steps of glycolysis. For such a purpose, the modelling of alpha- and beta-D-glucose catabolism, itself based on available information concerning both the utilisation of these two anomers and the intrinsic properties of phosphoglucoisomerase, was first examined. According to a theoretical model with enzyme-to-enzyme channelling, the generation of 3HOH from D-[2-3H]glucose should be higher in islets exposed to beta-D-glucose rather than alpha-D-glucose, whilst the opposite situation should prevail in the case of D-[5-3H]glucose conversion to 3HOH. Experimental data collected in rat islets incubated for 60 min at 4 degrees C in the presence of either alpha- or beta-D-glucose mixed with tracer amounts of either alpha- or beta-D-[2- 3H]glucose and alpha- or beta-D-[5-3H]glucose indicate that the beta/alpha ratio for D-[2-3H]glucose conversion to 3HOH is indeed higher than the beta/alpha ratio for D-[5-3H]glucose conversion to 3HOH. These findings are consistent with the postulated enzyme-to-enzyme tunnelling of glycolytic intermediates between hexokinase isoenzyme(s), phosphoglucoisomerase and, possibly, phosphofructokinase.

Metabolism of tritiated D-glucose anomers in rat erythrocytes.

It was recently proposed that alpha-D-glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-glucose but not significantly different from unity in the presence of beta-D-glucose. These findings emphasize the relevance of alpha-D-glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-glucose in distinct cell types.

Metabolism of D-glucose anomers in rat pancreatic islets exposed to equilibrated D-glucose.

This study aims at establishing the contribution of alpha- and beta-D-glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-glucose at anomeric equilibrium, the metabolic fate of alpha-D-glucose differs vastly from that of beta-D-glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-glucose 6-phosphate.

Labelling of lipids by D-[1-14C]glucose, D-[6-14C] glucose and D-[3-3H]glucose in pancreatic islets from normal and GK rats.

In pancreatic islets prepared from either normal or GK rats and incubated at either low (2.8 mM) or high (16.7 mM) D-glucose concentration, the labelling of both lipids and their glycerol moiety is higher in the presence of D-[1-14C]glucose than D-[6-14C]glucose. The rise in D-glucose concentration augments the labelling of lipids, the paired 14C/3H ratio found in islets exposed to both D-[1-14C]glucose or D-[6-14C]glucose and D-[3-3H]glucose being even slightly higher at 16.7 mM D-glucose than that found, under otherwise identical conditions, at 2.8 mM D-glucose. Such a paired ratio exceeds unity in islets exposed to D-[1-14C]glucose. The labelling of islet lipids by D-[6-14C]glucose is about 30 times lower than the generation of acidic metabolites from the same tracer. These findings indicate (i) that the labelling of islet lipids accounts for only a minor fraction of D-glucose catabolism in pancreatic islets, (ii) a greater escape to L-glycerol-3-phosphate of glycerone-3-phosphate generated from the C1-C2-C3 moiety of D-glucose than D-glyceraldehyde-3-phosphate produced from the C4-C5-C6 moiety of the hexose, (iii) that only a limited amount of [3-3H]glycerone 3-phosphate generated from D-[3-3H]glucose is detritiated at the triose phosphate isomerase level before being converted to L-glycerol-3-phosphate, and (iv) that a rise in D-glucose concentration results in an increased labelling of islet lipids, this phenomenon being somewhat more pronounced in the case of D-[1-14C]glucose or D-[6-14C]glucose rather than D-[3-3H]glucose.

Metabolic interactions between D-glucose and D-fructose in pancreatic islets

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Uptake of tritiated D-mannoheptulose by liver, pancreatic exocrine and endocrine cells.

Tritiated D-mannoheptulose, a ketoheptose known to inhibit D-glucose metabolism in hepatocytes and pancreatic islets, but not so in pancreatic acinar cells, was injected intravenously in streptozotocin-induced diabetic mice transplanted under the kidney capsule with islets from control mice of the same strain. One hour after the injection of the tritiated heptose, the radioactive content was 5-8 times higher in the liver and transplanted islets than in the pancreatic gland. It is proposed that suitably radiolabelled D-mannoheptulose could be used to label preferentially the endocrine moiety of the pancreatic gland, e.g., in the perspective of its non-invasive imaging.

Uptake of D-mannoheptulose by rat erythrocytes, hepatocytes and parotid cells.

D-[3H]mannoheptulose (or D-[1-14C] mannoheptulose) net uptake was measured in rat erythrocytes, parotid cells and hepatocytes. In the erythrocytes and parotid cells, the intracellular distribution space of the heptose (0.1 mM) represented only about 1 and 13%, respectively, of the intracellular 3HOH space. In hepatocytes, however, it amounted to approximately 45% of the intracellular 3HOH space. In all cases, the apparent distribution space of D-[3H]mannoheptulose hexaacetate largely exceeded that of unesterified D-[3H]mannoheptulose. Relative to the intracellular water space, the generation of acidic metabolites (expressed as an apparent distribution space) from radioactive D-mannoheptulose was one order of magnitude lower in parotid cells (< or = 3%) than in hepatocytes (> or = 20%). These findings are compatible with the hypothesis that D-mannoheptulose is transported into cells mainly, if not exclusively, at the intervention of GLUT2.

Inhibitory effect of lactoperoxidase-generated hypothiocyanite upon black pigmented anaerobe growth.

This study aimed to evaluate the in vitro effect of lactoperoxidase with or without its substrates (hydrogen peroxide, thiocyanate) on the growth of 4 different black pigmented anaerobe (BPA) strains associated with the development and progress of periodontal diseases: Porphyromonas gingivalis ATCC 33277, Prevotella intermedia NCTC 9336, Prevotella loescheii ATCC 15930, and Prevotella melaninogenica NCTC 9338. A 5-min lactoperoxidase-generated OSCN--HOSCN incubation at pH 6.0, 7.0 or 8.0 resulted in a decrease of the growth rate (tested by turbidimetry in liquid cultures) of the 4 BPA strains, whilst lactoperoxidase alone actually promoted bacterial growth.

Uptake of 1-deoxy-1-[125I]iodo-D-mannoheptulose by different cell types: in vitro and in vivo experiments.

D-mannoheptulose was recently proposed as a tool to label preferentially insulin-producing cells in the pancreatic gland in the perspective of the non-invasive imaging of the endocrine pancreas. In such a perspective, we have now synthesized 1-deoxy-1-[125I]iodo-D-mannoheptulose ([125I]MH) and examined its uptake by different rat cell types. No phosphorylation of [125I]MH by bovine heart hexokinase could be detected. The apparent distribution space of [125I]MH largely exceeded that of [U-14C]sucrose, considered as an extracellular marker, in erythrocytes, parotid cells, hepatocytes, pancreatic pieces and isolated pancreatic islets. Relative to the mean intracellular distribution space of 3HOH, that of [125I]MH was not significantly different in pancreatic pieces from either normal rats or streptozotocin-induced diabetic animals (STZ rats). In pancreatic islets, the uptake of [125I]MH was decreased at low temperature, but failed to be significantly affected by cytochalasin B. Sixty min after the intravenous injection of [125I]MH, the radioactive content of selected organs displayed the following hierarchy: muscle

Human macrophage tumor necrosis factor (TNF)-alpha production induced by Trypanosoma brucei gambiense and the role of TNF-alpha in parasite control.

Trypanosoma brucei gambiense, a causative agent of sleeping sickness, induced a dose-dependent production of tumor necrosis factor (TNF)-alpha by human macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell line, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-alpha. The addition of anti-TNF-alpha to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrelevant antibodies had no effect. TNF-alpha may have a direct role (i.e., direct trypanolytic activity) and/or an indirect one, such as TNF-alpha-mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-alpha on purified parasites was observed. This lytic effect was inhibited by anti-TNF-alpha. These data suggest that, as in experimental trypanosomiasis, TNF-alpha is involved in parasite growth control in human African trypanosomiasis.

D-mannoheptulose phosphorylation by hexokinase isoenzymes.

D-mannoheptulose is a specific inhibitor of D-glucose phosphorylation by hexokinase isoenzymes. In the present study, the phosphorylation of this heptose was investigated by either a spectrophotometric or radioisotopic procedure. Using yeast hexokinase, the phosphorylation of 25 mM D-mannoheptulose only represented 0.02% of that of 5 mM D-glucose. Such a percentage was increased to 3.93% in the case of bovine heart hexokinase. In the latter case, the Km for D-mannoheptulose was close to 0.2 mM and both D-glucose (0.1-1.0 mM) and D-glucose 6-phosphate (also 0.1-1.0 mM) inhibited the phosphorylation of the heptose (0.03-0.60 mM). Human B-cell glucokinase also catalyzed the phosphorylation of D-mannoheptulose (0.1 mM), which was now increased in a bell-shaped manner by D-glucose (1.0-20 mM). Likewise, rat parotid gland, liver and pancreatic islet homogenates catalyzed the phosphorylation of D-[3H]mannoheptulose. The results obtained in these three tissues differed from one another by their absolute values (per mg wet wt.), relative values (by reference to the phosphorylation rate of 10 mM D-glucose), and sensitivity to inhibition by D-glucose (10 mM).

Comparative cerebrospinal fluid diffusion of imipenem and meropenem in rats.

The main objective of this study was to compare the cerebrospinal fluid (CSF) diffusion of imipenem and meropenem at steady state, following intravenous infusions at various rates in rats. A preliminary experiment was conducted to estimate the elimination half-lives of these two carbapenem antibiotics, and then to evaluate the infusion duration necessary to reach steady state. CSF diffusion of imipenem was essentially linear over the wide range of infusion rates (66-1,320microg min(-1)) and corresponding steady-state plasma concentrations (11.7-443.0 microg mL(-1)). Conversely the CSF diffusion of meropenem was saturable, with a predicted maximum CSF concentration equal to 1.3 microg mL(-1). Extrapolation of these data to the clinical situation may not be possible since the rats had normal blood-brain and blood-CSF barriers whereas patients with diseases such as meningitis may not. However, it is suggested that the observed differences in the diffusion characteristics of imipenem and meropenem may be partly responsible for their differences in toxicity and efficacy at the central level.