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Hoe onvoorspelbaar is barbituraatdrank als hulp bij zelfdoding? De Richtlijn uitvoering euthanasie en hulp bij zelfdoding adviseert voorzichtigheid met deze methode vanwege onvoorspelbaarheden. Is de terughoudendheid terecht of verdient hulp bij zelfdoding in bepaalde gevallen toch de voorkeur boven euthanasie?

Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30 degrees C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05mumol/L for disaccharides and 0.1mumol/L for monosaccharides. Linearity for each probe was between 1 and 1000mumol/L (R(2): 0.9987-0.9999). Coefficients of variation were

VAN WIJCK, K., K. A. P. WIJNANDS, D. M. MEESTERS, B. BOONEN, L. J. C. VAN LOON, W. A. BUURMAN, C. H. C. DEJONG, K. LENAERTS, and M. POEZE. L-Citrulline Improves Splanchnic Perfusion and Reduces Gut Injury during Exercise. Med. Sci. Sports Exerc., Vol. 46, No. 11, pp. 2039–2046, 2014. Purpose: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. Methods: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. Results: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 T 142.3 HM) and arginine levels (238.5 T 9.1 HM) compared with that in placebo (45.7 T 4.8 HM and 101.5 T 6.1 HM, respectively, P G 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P G 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 T 6.0 vs j2.0 T 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0–60 min, j185% T 506% vs 1318% T 553%, P G 0.01). No significant differences were observed for intestinal permeability. Conclusions: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise.

Background & aims: Increased gastrointestinal (GI) permeability is an important hallmark of many conditions, potentially leading to antigen exposure and sepsis. Current permeability tests are hampered by analytical limitations. This study aims to compare the accuracy of our multi-sugar (MS) and the classical dual sugar (DS) test for detection of increased GI permeability. Methods: Ten volunteers received permeability analysis using MS (1 g sucrose, lactulose, sucralose, erythritol, 0.5 g rhamnose in water) or DS (5 g lactulose, 0.5 g rhamnose), after indomethacin or placebo. Blood and urine were analyzed by isocratic LC-MS. Results: MS testing revealed significantly elevated urinary lactulose/rhamnose (L/R) ratios after indomethacin, due to enhanced lactulose excretion (P

VAN WIJCK, K., K. LENAERTS, A. A. VAN BIJNEN, B. BOONEN, L. J. C. VAN LOON, C. H. C. DEJONG, and W. A. BUURMAN. Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes. Med. Sci. Sports Exerc., Vol. 44, No. 12, pp. 2257–2262, 2012. Introduction: Nonsteroidal anti-inflammatory drugs are commonly used by athletes to prevent anticipated exercise-induced pain, thereby putatively improving physical performance. However, these drugs may have potentially hazardous effects on the gastrointestinal (GI) mucosa during strenuous physical exercise. The aim of the current study was to determine the effect of oral ibuprofen administration before exercise on GI integrity and barrier function in healthy individuals. Methods: Nine healthy, trained men were studied on four different occasions: 1) 400 mg ibuprofen twice before cycling, 2) cycling without ibuprofen, 3) 400 mg ibuprofen twice at rest, and 4) rest without ibuprofen intake. To assess small intestinal injury, plasma intestinal fatty acid binding protein (I-FABP) levels were determined, whereas urinary excretion of orally ingested multisugar test probes was measured using liquid chromatography and mass spectrometry to assess GI permeability. Results: Both ibuprofen consumption and cycling resulted in increased I-FABP levels, reflecting small intestinal injury. Levels were higher after cycling with ibuprofen than after cycling without ibuprofen, rest with ibuprofen, or rest without ibuprofen (peak I-FABP, 875 T 137, 474 T 74, 507 T 103, and 352 T 44 pgImLj1 , respectively, P G 0.002). In line, small intestinal permeability increased, especially after cycling with ibuprofen (0–2 h urinary lactulose/rhamnose ratio, 0.08 (0.04–0.56) compared with 0.04 (0.00–0.20), 0.05 (0.01–0.07), and 0.01 (0.01–0.03), respectively), reflecting loss of gut barrier integrity. Interestingly, the extent of intestinal injury and barrier dysfunction correlated significantly (RS = 0.56, P G 0.001). Conclusion: This is the first study to reveal that ibuprofen aggravates exercise-induced small intestinal injury and induces gut barrier dysfunction in healthy individuals. We conclude that nonsteroidal anti-inflammatory drugs consumption by athletes is not harmless and should be discouraged. Key Words: NSAID, EXERCISE, GASTROINTESTINAL DAMAGE, PERMEABILITY

Physical exercise places high demands on the adaptive capacity of the human body. Strenuous physical performance increases the blood supply to active muscles, cardiopulmonary system, and skin to meet the altered demands for oxygen and nutrients. The redistribution of blood flow, necessary for such an increased blood supply to the periphery, significantly reduces blood flow to the gut, leading to hypoperfusion and gastrointestinal (GI) compromise. A compromised GI system can have a negative impact on exercise performance and subsequent postexercise recovery due to abdominal distress and impairments in the uptake of fluid, electrolytes, and nutrients. In addition, strenuous physical exercise leads to loss of epithelial integrity, which may give rise to increased intestinal permeability with bacterial translocation and inflammation. Ultimately, these effects can deteriorate postexercise recovery and disrupt exercise training routine. This review provides an overview on the recent advances in our understanding of GI physiology and pathophysiology in relation to strenuous exercise. Various approaches to determine the impact of exercise on the individual athlete's GI tract are discussed. In addition, we elaborate on several promising components that could be exploited for preventive interventions.

Contains fulltext : 96903.pdf (Publisher’s version ) (Open Access) 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-a)pCO(2) from -0.85+/-0.15 to 0.85+/-0.42 kPa (p

Contains fulltext : 89807.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To improve diagnosis of necrotizing enterocolitis (NEC) by noninvasive markers representing gut wall integrity loss (I-FABP and claudin-3) and gut wall inflammation (calprotectin). Furthermore, the usefulness of I-FABP to predict NEC severity and to screen for NEC was evaluated. METHODS: Urinary I-FABP and claudin-3 concentrations and fecal calprotectin concentrations were measured in 35 consecutive neonates suspected of NEC at the moment of NEC suspicion. To investigate I-FABP as screening tool for NEC, daily urinary levels were determined in 6 neonates who developed NEC out of 226 neonates included before clinical suspicion of NEC. RESULTS: Of 35 neonates suspected of NEC, 14 developed NEC. Median I-FABP, claudin-3, and calprotectin levels were significantly higher in neonates with NEC than in neonates with other diagnoses. Cutoff values for I-FABP (2.20 pg/nmol creatinine), claudin-3 (800.8 INT), and calprotectin (286.2 microg/g feces) showed clinically relevant positive likelihood ratios (LRs) of 9.30, 3.74, 12.29, and negative LRs of 0.08, 0.36, 0.15, respectively. At suspicion of NEC, median urinary I-FABP levels of neonates with intestinal necrosis necessitating surgery or causing death were significantly higher than urinary I-FABP levels in conservatively treated neonates. Of the 226 neonates included before clinical suspicion of NEC, 6 developed NEC. In 4 of these 6 neonates I-FABP levels were not above the cutoff level to diagnose NEC before clinical suspicion. CONCLUSIONS: Urinary I-FABP levels are not suitable as screening tool for NEC before clinical suspicion. However, urinary I-FABP and claudin-3 and fecal calprotectin are promising diagnostic markers for NEC. Furthermore, urinary I-FABP might also be used to predict disease severity. 01 juni 2010