Salivary concentrations of secretory leukocyte protease inhibitor and matrix metallopeptidase-9 following a single bout of exercise are associated with intensity and hydration status.

Aim: To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status.

Methods: Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5).

Flood Control: How Milk-Derived Extracellular Vesicles Can Help to Improve the Intestinal Barrier Function and Break the Gut-Joint Axis in Rheumatoid Arthritis.

Unlabelled: Many studies provided compelling evidence that extracellular vesicles (EVs) are involved in the regulation of the immune response, acting as both enhancers and dampeners of the immune system, depending on the source and type of vesicle. Research, including ours, has shown anti-inflammatory effects of milk-derived EVs, using human breast milk as well as bovine colostrum and store-bought pasteurized cow milk, in systems as well as therapeutically in animal models. Although it is not completely elucidated which proteins and miRNAs within the milk-derived EVs contribute to these immunosuppressive capacities, one proposed mechanism of action of the EVs is the modulation of the crosstalk between the (intestinal) microbiome and their host health.

Kinetics of Physiological Responses as a Measure of Intensity and Hydration Status During Experimental Physical Stress in Human Volunteers.

Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person's training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality.

Plasma citrulline concentration, a marker for intestinal functionality, reflects exercise intensity in healthy young men.

Background & Aims: Plasma citrulline concentration is considered to be a marker for enterocyte metabolic mass and to reflect its reduction as may occur during intestinal dysfunction. Strenuous exercise can act as a stressor to induce small intestinal injury. Our previous studies suggest that this comprises the intestinal ability to produce citrulline from a glutamine-rich protein bolus.

Specific prebiotic oligosaccharides modulate the early phase of a murine vaccination response.

The immune-modulatory effect of specific prebiotic oligosaccharides was shown in previous preclinical and clinical studies. To enhance the understanding of this effect, kinetic aspects of immune modulation and the correlation between microbiological and immunological parameters were investigated in a murine vaccination model. C57BL/6 mice were supplemented with short-chain galactooligosaccharides and long-chain fructooligosaccharides (ratio 9:1; Immunofortis()) in combination with pectin-derived acidic oligosaccharides.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis.

A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy.

Background: It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6 months of age in infants at risk for allergy.

Aim Of The Study: This study was aimed to analyze the effect of GOS/FOS on the immune response in these infants.

Dietary supplementation with specific oligosaccharide mixtures decreases parameters of allergic asthma in mice.

Specific mixtures of prebiotic oligosaccharides showed immune modulatory effects in previous murine vaccination experiments, suggesting a shift towards T-helper 1 (Th1) immunity. These mixtures consisted of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) in a 9:1 ratio (Immunofortis), with or without pectin-derived acidic oligosaccharides (pAOS). To investigate whether these mixtures could suppress Th2-related responses, they were tested in an ovalbumin (OVA)-induced model for experimental allergic asthma in BALB/c mice.

Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates.

Orally applied nondigestible carbohydrates (NDC) have been associated with immune-modulating effects and other health benefits. The effects of prebiotic carbohydrates have recently received much attention, but other NDC have been reported to induce immune modulation as well. Many different effects have been shown on parameters of innate and specific immunity, mostly in animal experiments or in vitro.

Dietary supplementation of neutral and acidic oligosaccharides enhances Th1-dependent vaccination responses in mice.

Immunomodulatory effects of oligosaccharide preparations that resemble chemical and functional aspects of human milk oligosaccharides (HMOS) were studied for the development of new concepts in infant nutrition. A dose range of 1-5% (w/w) dietary pectin-derived acidic oligosaccharides (AOS) was tested in a murine influenza vaccination model. In addition, combinations of AOS and a 9:1 mixture of galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) were tested at a fixed total dietary dose of 2% (w/w).

A specific prebiotic oligosaccharide mixture stimulates delayed-type hypersensitivity in a murine influenza vaccination model.

Analogous to reported immunomodulatory effects of probiotics, this study was performed to analyse the immunomodulatory properties of prebiotic oligosaccharides that share chemical characteristics with human milk oligosaccharides. A mixture containing galacto- and fructo-oligosaccharides (GOS/FOS; ratio 9:1) was tested at dietary doses between 1% and 10% (w/w of total diet) in an influenza vaccination model, using 10 C56BL/6JolaHsd mice per group. The modulation of vaccine specific delayed-type hypersensitivity (DTH) responses was studied as a marker of T-helper 1 (Th1) immunity, as well as other immune parameters.

Characterization of T cell epitopes in alphas1-casein in cow's milk allergic, atopic and non-atopic children.

Background: One to two percent of infants suffer from IgE-mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance.

Preoperative feeding preserves heart function and decreases oxidative injury in rats.

Objective: The nutritional status of a patient has been implicated as an important factor in the development of postoperative complications. Fasting before an operation may have detrimental effects on the metabolic state. We hypothesized that there was a positive correlation between preoperative nutritional status and postoperative organ function.

The influence of different combinations of gamma-linolenic acid, stearidonic acid and EPA on immune function in healthy young male subjects.

To determine the effects of EPA, stearidonic acid (STA) or gamma-linolenic acid (GLA) on immune outcomes, healthy male subjects consumed one of seven oil blends for 12 weeks. EPA consumption increased the EPA content of peripheral blood mononuclear cells (PBMC). Consumption of GLA (2.

Lactoferrin reduces methotrexate-induced small intestinal damage, possibly through inhibition of GLP-2-mediated epithelial cell proliferation.

A strategy protecting the small intestine against deleterious side effects associated with anti-cancer therapy is arresting epithelial cell cycling temporally. Since endogenous glucagon-like peptide-2 (GLP-2) is a trophic factor specific for intestinal epithelia, the possibility of inhibiting GLP-2-mediated cell proliferation by lactoferrin, thereby protecting the small intestine against deleterious side effects of anticancer therapy, was investigated. In Caco-2 cells, GLP-2-mediated proliferation was reduced in a dose-dependent manner using lactoferrin.

Measuring mucosal damage induced by cytotoxic therapy.

We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnosed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Gut integrity was already disturbed in the AML/MDS group as measured by the lactulose/rhamnose ratio (L/R ratio=0.09) before therapy and was severely perturbed (L/R ratio >0.

Role of curcumin and the inhibition of NF-kappaB in the onset of chemotherapy-induced mucosal barrier injury.

The inhibition of nuclear factor kappa B (NF-kappaB) by, for instance, curcumin is becoming an important new approach in combination with chemotherapy or irradiation for the treatment of a variety of cancers including haematological malignancies. A dose-limiting side effect of anticancer therapy in the gastrointestinal tract is mucosal barrier injury. It is hypothesised that mucosal barrier injury is initiated and amplified by proinflammatory-and NF-kappaB-regulated mediators.

Dihomo-gamma-linolenic acid inhibits tumour necrosis factor-alpha production by human leucocytes independently of cyclooxygenase activity.

Dietary oils (such as borage oil), which are rich in gamma-linolenic acid (GLA), have been shown to be beneficial under inflammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids.

Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids.

The flavonoid family shows a high potential for inhibition of xanthine oxidase. Currently, more than 4,000 flavonoids are known. The data of this study indicate that a planar structure is necessary for high inhibitory activity towards xanthine oxidase.

The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype.

The production of inflammatory mediators, relevant to (auto)immune diseases and chronic inflammatory conditions, can be modulated by dietary intake of n-3 and n-6 long chain polyunsaturated fatty acids (PUFAs). It was suggested that these effects are related to the formation of different series of eicosanoids, in particular prostaglandin-E (PGE). In this study we investigated whether prostaglandin subtypes metabolized from arachidonic acid (PGE2), dihomo-gamma-linolenic acid (PGE1) or eicosapentaenoic acid (PGE3) have different effects on T-cell proliferation and cytokine production in vitro.

Transforming Growth Factor-beta2 protects the small intestine during methotrexate treatment in rats possibly by reducing stem cell cycling.

During chemo- and radiation therapy, the balance between epithelial cell proliferation, differentiation, and cell death at the villus tip is disrupted by premature death of dividing epithelial cells. This will subsequently lead to the onset of mucosal barrier injury in the whole gastrointestinal tract. Up till now there is no validated method to treat side effects occurring due to therapy.

Differential fMet-Leu-Phe- and platelet-activating factor-induced signaling toward Ral activation in primary human neutrophils.

We have measured the activation of the small GTPase Ral in human neutrophils after stimulation with fMet-Leu-Phe (fMLP), platelet activating factor (PAF), and granulocyte macrophage-colony stimulating factor and compared it with the activation of two other small GTPases, Ras and Rap1. We found that fMLP and PAF, but not granulocyte macrophage-colony stimulating factor, induce Ral activation. All three stimuli induce the activation of both Ras and Rap1.

Activation of the small GTPase rap1 in human neutrophils.

The small GTPase Rap1 is highly expressed in human neutrophils, but its function is largely unknown. Using the Rap1-binding domain of RalGDS (RalGDS-RBD) as an activation-specific probe for Rap1, we have investigated the regulation of Rap1 activity in primary human neutrophils. We found that a variety of stimuli involved in neutrophil activation, including fMet-Leu-Phe (fMLP), platelet-activating factor (PAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IgG-coated particles, induce a rapid and transient Rap1 activation.