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Maastricht, Netherlands

Wijnands K.A.P.,Maastricht University | Vink H.,Maastricht University | Vink H.,CARIM Cardiovascular Research Institute of Maastricht | Briede J.J.,Maastricht University | And 5 more authors.
PLoS ONE | Year: 2012

Background: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. Methodology/Principal Findings: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 μg•g bodyweight-1•h-1), combined with either L-Citrulline (6.25 mg•h-1), L-Arginine (6.25 mg•h-1), or L-Alanine (isonitrogenous control; 12.5 mg•h-1) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. Conclusion/Significance: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability. © 2012 Wijnands et al.


Leenders M.,Top Institute Food and Nutrition | Verdijk L.B.,Top Institute Food and Nutrition | van der Hoeven L.,Top Institute Food and Nutrition | van Kranenburg J.,Top Institute Food and Nutrition | And 4 more authors.
Journal of Nutrition | Year: 2011

The loss of muscle mass with aging has been, at least partly, attributed to a blunted muscle protein synthetic response to food intake. Leucine coingestion has been reported to stimulate postprandial insulin release and augment postprandial muscle protein accretion. We assessed the clinical benefits of 6 mo of leucine supplementation in elderly, type 2 diabetes patients. Sixty elderly males with type 2 diabetes (age, 71 ± 1 y; BMI, 27.3 ± 0.4 kg/m2) were administered 2.5 g L-leucine (n = 30) or a placebo (n = 30) with each main meal during 6 mo of nutritional intervention (7.5 g/d leucine or placebo). Body composition, muscle fiber characteristics, muscle strength, glucose homeostasis, and basal plasma amino acid and lipid concentrations were assessed prior to, during, and after intervention. Lean tissue mass did not change or differ between groups and at 0, 3, and 6 mo were 61.9 ± 1.1, 62.2 ± 1.1, and 62.0 ± 1.0 kg, respectively, in the leucine group and 62.2 ± 1.3, 62.2 ± 1.3, and 62.2 ± 1.3 kg in the placebo group. There also were no changes in body fat percentage, muscle strength, and muscle fiber type characteristics. Blood glycosylated hemoglobin did not change or differ between groups and was 7.1 ± 0.1% in the leucine group and 7.2 ± 0.2% in the placebo group. Consistent with this, oral glucose insulin sensitivity and plasma lipid concentrations did not change or differ between groups. We conclude that prolonged leucine supplementation (7.5 g/d) does not modulate body composition, muscle mass, strength, glycemic control, and/or lipidemia in elderly, type 2 diabetes patients who habitually consume adequate dietary protein. © 2011 American Society for Nutrition.


Cuzick J.,Cancer Research UK Research Institute | Glasier A.,Family Planning and WW Services | La Vecchia C.,University of Milan | Maraganore D.M.,NorthShore University HealthSystem | And 16 more authors.
Human Reproduction Update | Year: 2011

Background: Lifestyle changes around the time of menopause have the potential to impact on morbidity and eventual mortality. Here we review this topic to identify how such changes may improve health at perimenopause and beyond. Methods: Searches were performed in Medline and other databases. Each subject summary was presented to the ESHRE Workshop Group, where omissions or disagreements were resolved by discussion. Results: Body weight increases because the decline in physical activity during the perimenopause is greater than the concomitant decline in energy intake. It is imperative to stop smoking before menopause because the risk of acute myocardial infarction rises sharply thereafter. Cardiovascular events can be reduced by managing risk factors, such as hypertension and increased lipids and body weight. Breast cancer risk is increased to a similar extent by hormone use, decreased physical activity, increased calorie intake and alcohol use, all reflecting lifestyle decisions. Smoking, alcohol and exercise may increase or decrease risk of aging brain disorders, especially dementia and Parkinson's disease, while stress is consistently associated with increased risk and a prudent diet is consistently associated with reduced risk. Osteoarthritis frequency increases after 50 years of age and risk is elevated 3-fold by obesity, while risk of osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise. Conclusions: Lifestyle changes around the time of the perimenopause can reduce the likelihood and severity of heart disease and chronic illness in later years and the cost of care of elderly women. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


van Wijck K.,Top Institute Food and Nutrition | van Wijck K.,Maastricht University | Lenaerts K.,Top Institute Food and Nutrition | Lenaerts K.,Maastricht University | And 7 more authors.
PLoS ONE | Year: 2011

Background: Splanchnic hypoperfusion is common in various pathophysiological conditions and often considered to lead to gut dysfunction. While it is known that physiological situations such as physical exercise also result in splanchnic hypoperfusion, the consequences of flow redistribution at the expense of abdominal organs remained to be determined. This study focuses on the effects of splanchnic hypoperfusion on the gut, and the relationship between hypoperfusion, intestinal injury and permeability during physical exercise in healthy men. Methods and Findings: Healthy men cycled for 60 minutes at 70% of maximum workload capacity. Splanchnic hypoperfusion was assessed using gastric tonometry. Blood, sampled every 10 minutes, was analyzed for enterocyte damage parameters (intestinal fatty acid binding protein (I-FABP) and ileal bile acid binding protein (I-BABP)). Changes in intestinal permeability were assessed using sugar probes. Furthermore, liver and renal parameters were assessed. Splanchnic perfusion rapidly decreased during exercise, reflected by increased gap g-apCO 2 from -0.85±0.15 to 0.85±0.42 kPa (p<0.001). Hypoperfusion increased plasma I-FABP (615±118 vs. 309±46 pg/ml, p<0.001) and I-BABP (14.30±2.20 vs. 5.06±1.27 ng/ml, p<0.001), and hypoperfusion correlated significantly with this small intestinal damage (r S = 0.59; p<0.001). Last of all, plasma analysis revealed an increase in small intestinal permeability after exercise (p<0.001), which correlated with intestinal injury (r S = 0.50; p<0.001). Liver parameters, but not renal parameters were elevated. Conclusions: Exercise-induced splanchnic hypoperfusion results in quantifiable small intestinal injury. Importantly, the extent of intestinal injury correlates with transiently increased small intestinal permeability, indicating gut barrier dysfunction in healthy individuals. These physiological observations increase our knowledge of splanchnic hypoperfusion sequelae, and may help to understand and prevent these phenomena in patients. © 2011 van Wijck et al.


Oudhuis G.J.,NUTRIM School for Nutrition | Oudhuis G.J.,Erasmus Medical Center | Bergmans D.C.J.J.,Maastricht University | Verbon A.,NUTRIM School for Nutrition | Verbon A.,Erasmus Medical Center
Current Opinion in Critical Care | Year: 2011

PURPOSE OF REVIEW: In this era of increasing antimicrobial resistance, use of probiotics in infection prevention has brought new perspective. However, in 2008 the, until then considered, safe use of probiotics became an important topic after publication of a trial showing excess mortality in patients on probiotic prophylaxis. In this article, we review the concept of infection prevention by probiotics and the present knowledge of the efficacy of probiotics in prevention of infections among patients with abdominal diseases and in intensive care. Safety issues of probiotics will be discussed extensively. RECENT FINDINGS: Over 30 clinical trials with probiotics to prevent infections have been published, some of which were prematurely stopped recently. Studies with critically ill patients and patients with abdominal diseases showed conflicting results regarding the effects of probiotics on infection rates, as did meta-analyses. These studies are difficult to compare because different probiotics were used which all have different efficacy and safety profiles. SUMMARY: The efficacy of probiotics in infection prevention among critically ill patients is still not unequivocally determined. The safety profile differs per probiotic strain and should not be generalized towards other strains and patient populations. A well designed and well powered clinical trial with clear endpoints to demonstrate efficacy is warranted. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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