In vitro batch fermentation of (un)saturated homogalacturonan oligosaccharides.

Pectin, predominantly present within plant cell walls, is a dietary fiber that potentially induces distinct health effects depending on its molecular structure. Such structure-dependent health effects of pectin-derived galacturonic acid oligosaccharides (GalA-OS) are yet largely unknown. This study describes the influence of methyl-esterification and ∆4,5-unsaturation of GalA-OS through defined sets of GalA-OS made from pectin using defined pectinases, on the fermentability by individual fecal inocula. The metabolite production, OS utilization, quantity and size, methyl-esterification and saturation of remaining GalA-OS were monitored during the fermentation of GalA-OS. Fermentation of all GalA-OS predominantly induced the production of acetate, butyrate and propionate. Metabolization of unsaturated GalA-OS (uGalA-OS) significantly increased butyrate formation compared to saturated GalA-OS (satGalA-OS), while satGalA-OS significantly increased propionate formation. Absence of methyl-esters within GalA-OS improved substrate metabolization during the first 18 h of fermentation (99 %) compared to their esterified analogues (51 %). Furthermore, HPAEC and HILIC-LC-MS revealed accumulation of specific methyl-esterified GalA-OS, confirming that methyl-esterification delays fermentation. Fermentation of structurally distinct GalA-OS results in donor specific microbiota composition with uGalA-OS specifically stimulating the butyrate-producer Clostridium Butyricum. This study concludes that GalA-OS fermentation induces highly structure-dependent changes in the gut microbiota, further expanding their potential use as prebiotics.

Dietary fat induced chylomicron-mediated LPS translocation in a bicameral Caco-2cell model.

BACKGROUND: There is increasing evidence that dietary fat, especially saturated fat, promotes the translocation of lipopolysaccharide (LPS) via chylomicron production in the gut. Chylomicrons can subsequently transport LPS to other parts of the body, where they can induce low-grade chronic inflammation that is linked to various metabolic and gut-related diseases. To identify promising (food) compounds that can prevent or ameliorate LPS-related low-grade inflammation, we developed and optimized a bicameral in vitro model for dietary fat-induced LPS translocation that closely mimics the in vivo situation and facilitates high-throughput screening. METHODS: Caco-2 cells were cultured in monolayers and differentiated to a small intestinal phenotype in 21 days. Thereafter, optimal conditions for fat-induced chylomicron production were determined by apical exposure of Caco-2 cells to a dilution range of in vitro digested palm oil and sunflower oil, optionally preceded by a 1-week apical FBS deprivation (cultured without apical fetal bovine serum). Chylomicron production was assessed by measuring basolateral levels of the chylomicron-related marker apolipoprotein B. Next, LPS was coincubated at various concentrations with the digested oils, and fat-induced LPS translocation to the basolateral side was assessed. RESULTS: We found that dietary fat-induced LPS translocation in Caco-2 cells was optimal after apical exposure to digested oils at a 1:50 dilution in combination with 750 ng/mL LPS, preceded by 1 week of apical FBS deprivation. Coincubation with the chylomicron blocker Pluronic L81 confirmed that fat-induced LPS translocation is mediated via chylomicron production in this Caco-2 cell model. CONCLUSION: We developed a robust Caco-2 cell model for dietary fat-induced LPS translocation that can be used for high-throughput screening of (food) compounds that can reduce LPS-related low-grade inflammation.

[Geriatric rehabilitation care: Doing the right things right]. / Geriatrische Revalidatiezorg: De juiste dingen goed doen.

BACKGROUND: Geriatric rehabilitation concerns short-term integrated multidisciplinary care aimed at functional recovery and social participation for relatively frail elderly. Given the geriatric clients' complex care issues, nurses should possess sufficient and appropriate competencies in order to identify and assess the relevant symptoms and intervene effectively. Yet, nurses experience a certain apprehensiveness to perform their tasks and express difficulties in multidisciplinary communication and collaboration in a constructive manner. In addition to the client's and informal care giver's perception of their input in the geriatric rehabilitation process, this study provides an in-depth understanding of the way nurses perceive their role in geriatric rehabilitation. METHODS/DESIGN: This descriptive study entails a quantitative and a qualitative component. The quantitative component concerns questionnaires for clients, informal care givers, nurses, and team leaders. The qualitative component aims to obtain in-depth information (i. e. opinions, meanings, and reflections) with regard to the decision making process and the performance of the rehabilitation care by means of open-ended questions (in the questionnaire) and semi-structured interviews. RESULTS: Clients and informal care givers rate specific themes in geriatric rehabilitation in a more negative light than nurses and team leaders do. These themes concern the provision of information in the hospital (prior to admission in the rehabilitation facility), involvement in the draw-up of the treatment plan and rehabilitation goals, geriatric rehabilitation as a 24/7 activity, and taking into account the client's other life events. The latter three findings in particular, are caused by nurses' apprehensiveness to perform their tasks adequately. DISCUSSION: Nurses working in geriatric rehabilitation, experience apprehensiveness to perform their tasks adequately. Uncertainty about the client's reaction or fear of damaging the relationship of trust, results in nurses not involving the clients and informal care givers in the draw-up of the rehabilitation goals. Apprehensiveness also submerges as the lack of experience or specific competences in considering the client's other life events. The recommendations address these aspects in particular.

[INTEGRATED APPROACH TO PREVENT FUNCTIONAL DECLINE IN HOSPITALIZED ELDERLY]. / Integrale interventie ter voorkoming van functieverlies bij ouderen tijdens ziekenhuisopname: het Zorgprogramma voor Preventie en Herstel.

BACKGROUND: Hospital related functional decline in older patients is an underestimated problem. Thirty-five procent of 70-year old patients experience functional decline during hospital admission in comparison with pre-illness baseline. This percentage increases considerably with age. METHODS/DESIGN: To address this issue, the Vlietland Ziekenhuis in The Netherlands has implemented the Prevention and Reactivation Care Programme (PReCaP), an innovative program aimed at reducing hospital related functional decline among elderly patients by offering interventions that are multidisciplinary, integrated and goal-oriented at the physical, social, and psychological domains of functional decline. DISCUSSION: This paper presents a detailed description of the intervention, which incorporates five distinctive elements: (1) Early identification of elderly patients with a high risk of functional decline, and if necessary followed by the start of the reactivation treatment within 48 h after hospital admission; (2) Intensive follow-up treatment for a selected patient group at the prevention and Reactivation Centre; (3) Availability of multidisciplinary geriatric expertise; (4) Provision of support and consultation of relevant professionals to informal caregivers; (5) Intensive follow-up throughout the entire chain of care by a casemanager with geriatric expertise. Outcome and process evaluations are ongoing and results will be published in a series of forthcoming papers. This article is an edited translation of the previously published article 'Integrated approach to prevent functional decline in hospitalized elderly: the Prevention and Reactivation Care Program (PReCaP), BMC Geriatrics 2012;12:7, AJBM de Vos, KJE Asmus-Szepesi, TJEM Bakker, PL de Vreede, JDH van Wijngaarden, EW Steyerberg, JP Mackenbach, AP Nieboer.

Rapid EPA and DHA incorporation and reduced PGE2 levels after one week intervention with a medical food in cancer patients receiving radiotherapy, a randomized trial.

BACKGROUND & AIMS: In cancer patients, metabolic alterations, reduced immune competence and anti-cancer treatment can increase the risk of infections. A rapid-acting nutritional intervention might reduce this risk and support overall treatment. The present study investigated whether one week of intervention with a specific medical food led to fatty acid incorporation and functional immunological changes. METHODS: In a randomized, double-blind study, 38 cancer patients receiving radiotherapy consumed daily for one week 400 ml of specific medical food, which is high in protein and leucine, and enriched with fish oil and specific oligosaccharides (Active group), or iso-caloric/iso-nitrogenous product (Control group). Blood samples were taken at day 0 (baseline) and day 7. RESULTS: After one week of intervention, the incorporation of EPA and DHA in white blood cells was significantly higher in the Active group (2.6% and 2.6% of total fatty acids) compared to the Control group (1.0% and 2.2% of total fatty acids) (p < 0.001 and p < 0.05). Serum PGE2 levels decreased in the Active group and increased in the Control group (p < 0.01). No differences were observed on cytokine production in LPS-stimulated whole blood cultures. CONCLUSIONS: In cancer patients receiving radiotherapy, nutritional intervention with a specific medical food rapidly increased the percentage EPA and DHA in white blood cell phospholipids and reduced serum levels of the inflammatory mediator PGE2 within one week. CLINICAL REGISTRATION NUMBER: NTR2121.

Bridging between professionals in perinatal care: towards shared care in the Netherlands.

Relatively high perinatal mortality rates in the Netherlands have required a critical assessment of the national obstetric system. Policy evaluations emphasized the need for organizational improvement, in particular closer collaboration between community midwives and obstetric caregivers in hospitals. The leveled care system that is currently in place, in which professionals in midwifery and obstetrics work autonomously, does not fully meet the needs of pregnant women, especially women with an accumulation of non-medical risk factors. This article provides an overview of the advantages of greater interdisciplinary collaboration and the current policy developments in obstetric care in the Netherlands. In line with these developments we present a model for shared care embedded in local 'obstetric collaborations'. These collaborations are formed by obstetric caregivers of a single hospital and all surrounding community midwives. Through a broad literature search, practical elements from shared care approaches in other fields of medicine that would suit the Dutch obstetric system were selected. These elements, focusing on continuity of care, patient centeredness and interprofessional teamwork form a comprehensive model for a shared care approach. By means of this overview paper and the presented model, we add direction to the current policy debate on the development of obstetrics in the Netherlands. This model will be used as a starting point for the pilot-implementation of a shared care approach in the 'obstetric collaborations', using feedback from the field to further improve it.

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. Supplementation with two mixtures of scGOS/lcFOS and scGOS/lcFOS/pAOS at approximately 1% (w/w% net oligosaccharides) in the diet, starting two weeks before OVA sensitization and lasting until the end of the experiment, decreased of several parameters of allergic asthma. The OVA-induced airway inflammation and hyperresponsiveness was significantly suppressed by both mixtures. Moreover, OVA-specific IgE titers were decreased by more than 25%, although this effect was not significant. The effects of the oligosaccharide mixture with pAOS appeared to be more pronounced than the effects of the scGOS/lcFOS mixture without pAOS, but a direct comparison between the mixtures was not made. Overall, the results further support the hypothesis that specific mixtures of oligosaccharides modulate the Th1/Th2 balance by enhancing Th1-related and suppressing Th2-related parameters.

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. Data from clinical trials are limited, but promising studies have reported beneficial effects on mucosal and systemic immunity in humans. NDC are fermented to various degrees by the intestinal microbiota. Therefore, immune-modulatory properties have often been attributed to microbiota-dependent effects, especially in the case of prebiotic NDC. However, some NDC have been reported to bind to specific receptors on cells of the immune system, suggesting microbiota-independent, immune-modulatory effects play a role as well. This review aims to provide an overview of the published immune-modulatory effects in vitro and in vivo induced by NDC such as fructans, galactooligosaccharides, beta-glucans, pectins, and resistant starch. In addition, issues related to the underlying mechanisms are discussed: interaction between bacteria, their metabolites and the immune system, as well as direct effects of NDC via lectin receptors.

Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats.

BACKGROUND: Sepsis and endotoxemia are associated with concurrent activation of inflammation and the hemostatic mechanism, which both contribute to organ dysfunction and death. Electrical vagus nerve stimulation (VNS) has been found to inhibit tumor necrosis factor (TNF)-alpha release during endotoxemia in rodents. OBJECTIVE: To determine the effect of VNS on activation of coagulation and fibrinolysis. METHODS: Rats received a sublethal i.v. dose of lipopolysaccharide (LPS) after electrical VNS or sham stimulation. Activation of coagulation and fibrinolysis, as well as cytokine release, was measured before LPS injection and 2, 4 and 6 h thereafter. RESULTS: LPS induced activation of the coagulation system (increases in the plasma concentrations of thrombin-antithrombin complexes and D-dimer, and a decrease in antithrombin) and biphasic changes in the fibrinolytic system [early rises of plasminogen activator activity and tissue-type plasminogen activator, followed by a delayed increase in plasminogen activator inhibitor type 1 (PAI-1)]. VNS strongly inhibited all LPS-induced procoagulant responses and more modestly attenuated the fibrinolytic response. In addition, VNS attenuated the LPS-induced increases in plasma and splenic concentrations of the proinflammatory cytokines TNF-alpha and interleukin-6 (IL-6), while not influencing the release of the anti-inflammatory cytokine IL-10. CONCLUSION: These data illustrate a thus far unrecognized effect of VNS and suggest that the cholinergic anti-inflammatory pathway not only impacts on inflammation but also on the coagulant-anticoagulant balance.

The effect of supplementation with an enriched drink on indices of immune function in frail elderly.

Ageing induces a change in immune responses. Besides this, impaired nutritional status is considered to have a critical influence on immune function, which may be reversed by nutritional supplementation. We evaluated the effect of an enriched drink on immune function in the elderly. 33 frail elderly subjects (aged > or = 65 years and body mass index < or = 25) received two 125 ml packages of either an enriched drink (n=20) or placebo (n=13) daily for 6 months. The enriched drink contained macro- and micronutrients. At baseline and after 6 months blood samples were drawn and PBMC's were isolated. ConA stimulated proliferation and IL-2 production of PBMC's were measured. There was a significant difference between groups in proliferation over the study period. The supplement group remained stable whereas the placebo group showed a reduction in proliferation over the 6-month period. There was no significant difference in IL-2 production between groups. Our study adds to the evidence that nutritional supplementation can affect immune function in the elderly.

Origin of maternally transferred antibodies against rabies in foxes (Vulpes vulpes).

During previous experiments, maternal antibodies against rabies were detected in the sera of fox cubs whelped by orally immunised vixens. These antibodies appear to be transferred exclusively via the colostrum. No evidence of maternally transferred immunity in the form of immunoglobulin G was found in 80 fox embryos collected from 19 rabies-immune vixens originating from areas where oral rabies vaccine baits had been distributed.

In vitro effect of bioactive compounds on influenza virus specific B- and T-cell responses.

In vitro studies have demonstrated positive effects of bioactive compounds on several functions of the immune system. In the present study, 25 of such compounds were tested for their immune modulating properties on influenza virus specific human B- and T-cell responses in vitro. One of these compounds, N-acetyl-L-cysteine was shown to increase influenza virus specific lymphocyte proliferation and interferon(IFN)-gamma production at a concentration of 1.0 mmol/l. Furthermore, N-acetyl-L-cysteine was found to enhance a specific activity of two influenza specific CD8+ cytotoxic T-lymphocyte clones directed towards HLA-A*0201 and HLA-B*2705 restricted epitopes. A second compound, chlorogenic acid, was shown to enhance antigen specific proliferation of lymphocytes in three out of four donors, at concentrations of 10-50 micromol/l. Neither of the two compounds exhibited a positive effect on the production of influenza virus specific antibodies by human peripheral blood mononuclear cells in vitro.

Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors.

BACKGROUND: The prognosis of children who are affected by hepatoblastoma (HB) that presents with lung metastases has always been considered very poor. In light of the overall improvement in the survival of HB patients since the introduction of cisplatin (CDDP) in the therapeutic armament of this tumor, the question has been raised whether patients with metastatic HB also would benefit from this drug. The purpose of the current study was to address this issue by analyzing the treatment outcome of those patients presenting with metastases who entered into the first HB study on childhood liver tumors conducted by the International Society of Paediatric Oncology (SIOPEL 1). METHODS: SIOPEL 1 was a prospective, international, multicentric, single-arm study based on preoperative chemotherapy that was open to patient registration from January 1990 to February 1994. After undergoing a biopsy, patients received four courses of CDDP (80 mg/m(2) in a 24-hour, continuous infusion) on Day 1 followed by doxorubicin (60 mg/m(2) in a 48-hour, continuous infusion) on Days 2 and 3 (PLADO). Surgery was performed after four courses of PLADO and was followed by two more courses. Untreated children age < 16 years with biopsy-proven HB were eligible for the study. Metastatic spread was assessed by chest X-ray and, where available, lung computed tomography scan. RESULTS: Thirty-one of 154 children that entered into the trial presented with metastases. Eight children presently are alive with no evidence of disease (NED) after being treated with protocol therapy only (median follow-up, 60 months); nine children are alive with NED after having failed PLADO and having been rescued with alternative therapies (median follow-up, 80 months). The 5-year overall and event free survival rates for these children were 57% (95% confidence interval, 39-75%) and 28% (95% confidence interval, 12-44%), respectively. Persistent lung disease was the main reason for PLADO failure (17 of 23 patients; 74%). CONCLUSIONS: The SIOPEL 1 therapeutic strategy seems to cure 25% of the HB patients who present with metastases. However, further chemotherapy and the use of thoracotomies still can save significant numbers of these children.

The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.

Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase.

Pretreatment with [131I] metaiodobenzylguanidine and surgical resection of advanced neuroblastoma.

Pretreatment with [131I] metaiodobenzylguanidine (MIBG) followed by surgical resection in advanced neuroblastoma (stage 3 and 4) has been studied in relation to resectability, morbidity and mortality, survival rate after two years, control of distant metastasis and serum levels of LDH as prognostic factors. Twenty-one patients with advanced neuroblastoma were primarily treated with MIBG radiotherapy, followed by surgical resection. Sixteen patients had stage 4 disease. Between 2 and 6 courses of MIBG treatment were given per patient. In 17 patients gross complete resection was achieved. Two patients developed complications directly related to the operation, one died as a result of this. The overall mortality was 38%. MIBG therapy resulted in partial response in 13 patients and in stable disease in 8 patients. Two years survival in the group with partial response was 86% and in the group with stable disease 28%. Because of the resulting excellent general condition of the patients the interval between pretreatment with MIBG and surgery could be very short. Follow-up till December 1994 showed that 13 children were alive for 3 to 47 months. Seven had no evidence of disease. Preoperative MIBG de novo treatment in advanced neuroblastoma is equal to induction chemotherapy, but less toxic.

Antegrade colonic enema (ACE): a new therapeutic approach to chronic constipation.

Continent appendio-cecostomy is a recently developed operation for the therapy of chronic constipation, refractory for other treatment modalities. Two patients are described in whom the operation led to a dramatic improvement of their quality of life. Technical details of the operation are offered as well as some data on the possible mechanism of colonic motility in this pathological disorder.

Antegrade colonic enema (ACE): a new therapeutic approach to chronic constipation

Continent appendio-cecostomy is a recently developed operation for the therapy of chronic constipation, refractory for other treatment modalities. Two patients are describe in whom the operation led to a dramatic improvement of their quality of life. Technical detalis of the operation are offered as well as some data on the possible mechanism of colonic motility in this pathological disorder.

Antegrade colonic enema (ACE): a new therapeutic approach to chronic constipation

Continent appendio-cecostomy is a recently developed operation for the therapy of chronic constipation, refractory for other treatment modalities. Two patients are describe in whom the operation led to a dramatic improvement of their quality of life. Technical detalis of the operation are offered as well as some data on the possible mechanism of colonic motility in this pathological disorder. (AU)

[Experiences in the treatment of intestinal invagination in children]. / Ervaringen met de behandeling van invaginaties van de darm bij kinderen.

Intussusception is one of the more common causes of an acute abdomen in infancy. There is discussion about the appropriate method of treatment, and especially about the criteria for hydrostatic reduction. To evaluate the effectiveness of treatment of patients with intussusception presenting at the Paediatric Surgical Centre in Amsterdam, a retrospective study was carried out. 84 Cases were seen between 1980-1990. Three quarters of the children were operated, one-third without prior barium enema. In half the cases an attempt at hydrostatic reduction was made, and this succeeded in only 43%. Ultrasound was only rarely used diagnostically. The literature shows that the use of air to attempt reduction is more likely to be effective and less likely to cause complications than barium.