Importance of the brain corticosteroid receptor balance in metaplasticity, cognitive performance and neuro-inflammation.

Bruce McEwen's discovery of receptors for corticosterone in the rat hippocampus introduced higher brain circuits in the neuroendocrinology of stress. Subsequently, these receptors were identified as mineralocorticoid receptors (MRs) that are involved in appraisal processes, choice of coping style, encoding and retrieval. The MR-mediated actions on cognition are complemented by slower actions via glucocorticoid receptors (GRs) on contextualization, rationalization and memory storage of the experience. These sequential phases in cognitive performance depend on synaptic metaplasticity that is regulated by coordinate MR- and GR activation. The receptor activation includes recruitment of coregulators and transcription factors as determinants of context-dependent specificity in steroid action; they can be modulated by genetic variation and (early) experience. Interestingly, inflammatory responses to damage seem to be governed by a similarly balanced MR:GR-mediated action as the initiating, terminating and priming mechanisms involved in stress-adaptation. We conclude with five questions challenging the MR:GR balance hypothesis.

Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing.

BACKGROUND: Oral contraceptives (OCs) affect mood in some women and may have more subtle effects on emotional information processing in many more users. Female carriers of mineralocorticoid receptor (MR) haplotype 2 have been shown to be more optimistic and less vulnerable to depression. AIM: To investigate the effects of oral contraceptives on emotional information processing and a possible moderating effect of MR haplotype. METHODS: Cross-sectional study in 85 healthy premenopausal women of West-European descent. RESULTS: We found significant main effects of oral contraceptives on facial expression recognition, emotional memory and decision-making. Furthermore, carriers of MR haplotype 1 or 3 were sensitive to the impact of OCs on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. LIMITATIONS: Different compounds of OCs were included. No hormonal measures were taken. Most naturally cycling participants were assessed in the luteal phase of their menstrual cycle. CONCLUSIONS: Carriers of MR haplotype 2 may be less sensitive to depressogenic side-effects of OCs.

Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa.

5-hydroxytryptophan (5-HTP) is a direct 5-hydroxytryptamine (5-HT) precursor used to assess central serotonergic function. Its use has been limited by a narrow window between neuroendocrine changes and side effects, and variable kinetics related to inconsistent administration modes. By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT. A double-blind, placebo-controlled, single rising dose, four-way crossover trial with placebo randomisation was performed in 15 healthy male volunteers to investigate the neuroendocrine dose-response relationship at various 5-HTP levels; the tolerability and subjective effects of oral 5-HTP at 100, 200 and 300 mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge. Dose-dependent increases in average cortisol concentrations were observed. Mean response (area-under-the-curve) over the first 4 hours (SD): 172.0 nmol/L (22.3) for placebo, 258.3 nmol/L (72.6) for 100 mg, 328.47 nmol/L (84.6) for 200 mg and 387.3 nmol/L (82.4) for 300 mg 5-HTP. Similar dose-dependent increases for prolactin were seen while adreno-corticotrophic hormone response was more variable. 5-HTP kinetics were adequately described using a one-compartment model with first-order absorption and a lag time (mean oral clearance 28 L/h interindividual coefficient of variation 31%). Nausea and vomiting occurred dose-dependently as most frequent side effects, resulting in dose-related dropout of 6.6% at 100 mg and 45.5% at 300 mg 5-HTP. Orally administered 5-HTP combined with CBD is an effective serotonergic challenge test, exhibiting dose-related plasma concentrations and neuroendocrine responsiveness. Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100 mg.

Need for alternative ways of phenotyping of mood, anxiety, and somatoform disorders in biological research.

Variation in psychiatric symptomatology is continuous and does not coalesce into fairly well-defined categorical DSM-IV clusters. As a consequence, DSM-IV fails to meaningfully integrate information generated by neuroendocrine research. Continuous psychological dimensions selected for their predictiveness with respect to endophenotypes, as biological intermediate factors, are proposed to be the best ways in reaching an understanding of the causations in mood, anxiety, and somatoform disorders.

Active and intelligent packaging for food: is it the future?

This paper gives an overview of the legal consequences of a new EU framework regulation on food contact materials which includes controls on active and intelligent packaging. Recent developments in active and intelligent packaging systems are described, two examples of which aim at achieving improvements in quality and safety of food products. The first one is an on-command preservative-releasing packaging system. The second system is an intelligent concept, based on the development of a non-invasive microbial growth sensor to monitor the sterility of food products.

Evaluation of migration models that might be used in support of regulations for food-contact plastics.

Materials and articles intended to come into contact with food must be shown to be safe because they might interact with food during processing, storage and the transportation of foodstuffs. Framework Directive 89/109/EEC and its related specific Directives provide this safety basis for the protection of the consumer against inadmissible chemical contamination from food-contact materials. Recently, the European Commission charged an international group of experts to demonstrate that migration modelling can be regarded as a valid and reliable tool to calculate 'reasonable worst-case' migration rates from the most important food-contact plastics into the European Union official food simulants. The paper summarizes the main steps followed to build up and validate a migration estimation model that can be used, for a series of plastic food-contact materials and migrants, for regulatory purposes. Analytical solutions of the diffusion equation in conjunction with an 'upper limit' equation for the migrant diffusion coefficient, D(P), and the use of 'worst case' partitioning coefficients K(P,F) were used in the migration model. The results obtained were then validated, at a confidence level of 95%, by comparison with the available experimental evidence. The successful accomplishment of the goals of this project is reflected by the fact that in Directive 2002/72/EC, the European Commission included the mathematical modelling as an alternative tool to determine migration rates for compliance purposes.

Evaluating the migration of ingredients from active packaging and development of dedicated methods: a study of two iron-based oxygen absorbers.

The behaviour of two commercial oxygen-scavenging products with respect to migration of active ingredients into foodstuffs was investigated. Migrants were identified, and by using appropriate analytical methods, migration was determined in a variety of liquid, solid or gelled food simulants and foods. Simulants were chosen to cover a range of water activities and viscosities. Foods and the gelled food simulant agar were packed with and without vacuum, and with the oxygen scavenger in various locations relative to the packed food. The main migrants, as identified by X-ray fluorescence spectrometry, infrared spectroscopy and scanning electron microscopy with energy-dispersive spectrometry were Na(+) and Cl(-) in non-acidic aqueous simulants, and Na(+), Cl(-) and Fe(2+) in 3% acetic acid. Migration into aqueous simulants exceeded the current European Union limit for total migration from plastic materials (assumed to be currently applicable to these systems) and was probably excessive by any reasonable standard. However, neither oxygen scavenger appeared to release significant quantities of migrants into solid foods when the scavenger was properly located in the package and the packing process does not favour the contents becoming wet by water released from the food.

Active and intelligent packaging: applications and regulatory aspects.

Changes in the way foods are produced, distributed, stored and retailed, reflecting the continuing increase in consumer demands for improved quality and extended shelf-life for packaged foods, are placing ever-greater demands on the performance of food packaging. Consumers want to be assured that the packaging is fulfilling its function of protecting the integrity, quality, freshness and safety of foods. To provide this assurance and help improve the performance of the packaging, innovative active and intelligent packaging concepts are being developed and applied in various countries. In Europe, however, the development and application of active and intelligent packaging systems have been limited thus far. The main reasons are legislative restrictions and a lack of knowledge about consumer acceptance, the efficacy of such systems, and the economic and environmental impact they may have. Therefore, in 1999, a European study was started within the framework of the EU FAIR R&D programme. It aims to initiate amendments to European legislation for food-contact materials to establish and implement active and intelligent systems within the current relevant regulations for packaged food in Europe. This paper presents an overview of existing active and intelligent systems and their current and future food-related applications. In addition, developments and trends in active and intelligent food packaging are discussed. The objectives and the work programme of the European project are reviewed and the results obtained so far are presented. The benefits for both the European consumer and the European food and food-packaging industries are highlighted.

Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants.

The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.

Determination of paraffins in food simulants and packaging materials by liquid chromatography with evaporative mass detection and identification of paraffin type by liquid chromatography/gas chromatography and fourier transform infrared spectroscopy.

A liquid chromatographic method with evaporative mass detection (EMD) is described for the determination of paraffins in food contact materials that do not contain polyolefin oligomers, or paraffins migrating from these materials into fatty food simulants or certain simple foods. A normal-phase column operating at maximum column efficiency separates nonparaffinic and paraffinic materials without resolving the latter into individual components, and EMD is used to quantitate the paraffins. An on-line qualitative method that uses liquid chromatography/gas chromatography with flame ionization detection discriminates between paraffin waxes and oils in food contact materials, food simulants, and certain simple foods; a Fourier transform infrared spectrophotometric qualitative method also discriminates between waxes and oils, but is usually restricted to food contact materials that do not contain polyolefins and to migration experiments with organic solvents as fatty food simulants (with some other fatty food simulants, paraffin type must then be identified in the food contact material).

Stability of the Secondary Antioxidant Bis(2,4-di-tert-butylphenyl)pentaerythritol Diphosphite in Food Simulants.

To establish the stability of Ultranox 626 (an antioxidant added to plastics) in food simulants under migration conditions, migrations tests have been performed. A method has been developed for the determination of Ultranox 626 in the aqueous food simulants distilled water, 3% (w/v) acetic acid, and 15% (v/v) ethanol and in the fatty food simulants 95% (v/v) ethanol and isooctane. The method uses reversed-phase high-performance liquid chromatography with ultraviolet detection at 230 nm, is fast, and can be run automatically. To determine the stability of Ultranox 626, it was heated in each of the listed food simulants under the conditions stipulated in EU regulations for testing for compliance with migration limits. These experiments showed that this additive had acceptable stability in water, 15% and 95% (v/v) ethanol, and isooctane but that it decomposed completely in 3% (w/v) acetic acid. Migration testing with 3% acetic acid is of no use, since by the end of the testing regime the additive will have undergone substantial or total decomposition, and the level detected will not reflect the true level of migration. The EU Commission should replace 3% acetic acid with 15% ethanol as an appropriate test simulant for the determination of Ultranox 626 in all types of acid- and alcohol-containing foodstuffs. A number of experiments were carried out to develop a suitable method for the determination of Ultranox in fat simulants such as olive oil and HB 307. It appeared not possible, within the scope of this project, to obtain a method suitable to establish the stability of Ultranox 626 in fat simulants. Best results were obtained by freezing out the fat at -80 degrees C, but recovery was limited to 50%, which was insufficient for the intended purpose. Further experiments are required to establish the stability of Ultranox 626 in fat simulants such as olive oil and HB 307.

Glucocorticoids and immune function: unknown dimensions and new frontiers.

Despite the importance of glucocorticoids (GCs) to modern medicine, the physiological role of endogenous corticosteroids in immunomodulation is poorly understood. This article discusses evidence suggesting that endogenous GCs not only suppress but also direct and enhance immune functions. These often overlooked actions might well be more important than the inhibitory functions during host defence and the maintenance of homeostasis.

The suitability of alternative fatty food simulants for overall migration testing under both low- and high-temperature test conditions.

The suitability of various alternative, volatile fatty food simulants for overall migration testing was investigated under both low- and high-temperature test conditions. The overall migration into olive oil from a large number of commercially used food packaging materials applying various low- and high-temperature test conditions (e.g. 2 h at 175 degrees C, 30 min at 130 degrees C, 1 h at 100 degrees C followed by 10 days at 40 degrees C, 10 days at 20 degrees C) was determined. The results were compared with overall migration from these samples into iso-octane, 50% or 95% ethanol and isopropanol under appropriate test conditions. The samples investigated include homogeneous plastic films, laminates, coated board samples, a coated can, and articles. The results of the study indicate that iso-octane, 95% ethanol and isopropanol are suitable alternative fatty food simulants for overall migration testing under various time and temperature conditions.

Test methods to simulate high-temperature exposure.

A study was carried out to compare the actual overall migration from packaging materials into food simulants during heating in a microwave oven, and the overall migration from these materials into food simulants applying time and temperature conditions stipulated in the current EC and Dutch legislation on food packaging. It was demonstrated that the requirement by some food packaging regulations to conduct migration tests in a conventional oven using test conditions that are more stringent than the conditions occurring in practice results in excessively severe and unreasonable test conditions. On the basis of the results obtained additional test conditions (e.g. 30 min and 1 h in combination with test temperatures exceeding 121 degrees C, and a test temperature of 130 degrees C) are proposed to be inserted in existing food packaging regulations to enable realistic migration testing of microwave packaging materials under conventional test conditions. It is concluded that the overall migration behaviour of packaging materials intended for microwave oven use, including microwave-active (susceptor) materials, can be judged on the basis of migration testing using conventional heating. The suitability of iso-octane as a volatile fatty food simulant for the determination of the overall migration under high-temperature test conditions was also investigated. For most samples investigated a good agreement was observed between the overall migration values obtained with olive oil applying both microwave and conventional heating, and those obtained with iso-octane under conventional conditions.

Migration testing with olive oil in a microwave oven.

A study was carried out to compare the overall migration from packaging materials into olive oil during heating in a microwave oven, and the overall migration from the same materials into olive oil but applying time and temperature conditions stipulated in the current EC and Dutch legislation on food packaging. Application of additional test conditions (e.g. 30 min and 1 h in combination with test temperatures exceeding 121 degrees C, and a test temperature of 130 degrees C) have demonstrated the need for extension of the test conditions mentioned in existing food packaging regulations to enable realistic migration testing of microwave packaging materials under conventional test conditions. It is concluded that the overall migration into olive oil from packaging materials intended for microwave oven use, including susceptor materials, can be judged on the basis of migration testing using conventional heating. For testing film or susceptor materials in a microwave oven by one-sided contact, a migration cell transparent to microwaves was developed and used up to 200 degrees C. In conventional high-temperature tests applying hot-filling of trays or migration cells, a temperature drop was observed, while handling oil at temperatures of 150 degrees-175 degrees C may be considered perilous. To prevent problems of this kind it is proposed to start migration tests at room temperature and to heat the simulant rapidly to the final test temperature. This procedure is comparable to migration tests carried out with aqueous food simulants at 121 degrees C in an autoclave.(ABSTRACT TRUNCATED AT 250 WORDS)

Both interleukin-1 alpha and interleukin-1 beta are involved as accessory signals in primary antigen (tetanus toxoid) induced human T-cell activation.

The function of interleukin-1 alpha and interleukin-1 beta (IL-1 alpha, IL-1 beta) in tetanus toxoid (TT) induced T-cell proliferation in cultures of peripheral blood mononuclear cells (PBL) obtained from healthy donors was assessed by using neutralizing antisera to IL-1 alpha and IL-1 beta. The neutralizing capacity and the specificity of the IL-1 antisera were tested by the use of the thymoma EL-4 NOB-1 cell line. Antisera to IL-1 beta effectively neutralized the proliferative capacity of human recombinant IL-1 beta but not of human recombinant IL-1 alpha and vice versa. Addition of either anti-IL-1 beta or anti-IL-1 alpha antiserum to the culture medium hardly affected TT induced T-cell proliferation. However, the proliferative T-cell response was consistently attenuated when a combination of IL-1 alpha and IL-1 beta antiserum was used. The antisera were never capable of completely abolishing the T-cell response to TT. We conclude that (a) IL-1 alpha and IL-1 beta are both necessary accessory signals for T-cell proliferation to antigen in vitro; (b) in T-cell proliferation IL-1 alpha and IL-1 beta are interchangeable; and (c) T-cell proliferation to antigen is only partially dependent on IL-1 as signal.

Immunological characterization of Rhizobium leguminosarum outer membrane antigens by use of polyclonal and monoclonal antibodies.

Surface antigens of Rhizobium leguminosarum biovar viciae strain 248 were characterized by using polyclonal and monoclonal antibodies. With Western immunoblotting as the criterion, an antiserum raised against living whole cells recognized mainly flagellar antigens and the O-antigen-containing part of the lipopolysaccharide (LPS). Immunization of mice with a peptidoglycan-outer membrane complex yielded eight monoclonal antibodies, of which three reacted with LPS and five reacted with various sets of outer membrane protein antigens. The observation that individual monoclonal antibodies react with sets of related proteins is discussed. Studies of the influence of calcium deficiency and LPS alterations on surface antigenicity showed that in normally grown wild-type cells, the O-antigenic side chain of LPS blocks binding of an antibody to a deeper-lying antigen. This antigen is accessible to antibodies in cells grown under calcium limitation as well as in O-antigen-lacking mutant cells. Two of the antigen groups which can be distinguished in cell envelopes of free-living bacteria were depleted in cell envelopes of isolated bacteroids, indicating that the monoclonal antibodies could be useful tools for studying the differentiation process from free-living bacteria to bacteroids.