Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study

<p>Abstract</p> <p>Background</p> <p>It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also.</p> <p>Methods</p> <p>By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit^©L30D-55.</p> <p>Results</p> <p>Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022–0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035–0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033–0.065)) nor adenosine (0.050 (0.030–0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant.</p> <p>Conclusion</p> <p>In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.</p

Bioavailability of Iron, Zinc, Phytate and Phytase Activity during Soaking and Germination of White Sorghum Varieties

The changes in phytate, phytase activity and in vitro bioavailability of iron and zinc during soaking and germination of three white sorghum varieties (Sorghum bicolor L. Moench), named Dorado, Shandweel-6, and Giza-15 were investigated. Sorghum varieties were soaked for 20 h and germinated for 72 h after soaking for 20 h to reduce phytate content and increase iron and zinc in vitro bioavailability. The results revealed that iron and zinc content was significantly reduced from 28.16 to 32.16% and 13.78 to 26.69% for soaking treatment and 38.43 to 39.18% and 21.80 to 31.27% for germination treatments, respectively. Phytate content was significantly reduced from 23.59 to 32.40% for soaking treatment and 24.92 to 35.27% for germination treatments, respectively. Phytase enzymes will be activated during drying in equal form in all varieties. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the varieties used. The in vitro bioavailability of iron and zinc were significantly improved as a result of soaking and germination treatments

Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects

Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. [email protected] OBJECTIVE: The new uncoupling proteins, UCP2 and UCP3, are thought to play a role in energy efficiency in humans. Endurance training has been suggested to have effects on resting metabolic rate and energy efficiency. We therefore determined UCP2 and UCP3 mRNA levels in skeletal muscle of trained and untrained male subjects. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), expression of UCP2, UCP3L and UCP3S mRNA were measured in muscle biopsies from the quadriceps femoris in eight trained (23.9+/-1.6 y; 70.6+/-3.1 kg; 14+/-3% body fat; maximal power output (Wmax): 5. 6+/-0.4 W/kg; mean+/-s.d.) and 10 lean, untrained (22.1+/-2.9 y; 72. 0+/-7.9 kg; 18+/-4% body fat; Wmax: 3.9+/-0.4 W/kg; mean+/-s.d.) subjects. In six of the trained subjects, UCP2 and UCP3 mRNA were measured before and after an exercise bout to exhaustion. To correct for differences in mitochondrial content, levels of UCP2 and UCP3 mRNA were expressed relative to cytochrome-b, a marker of mitochondrial content. RESULTS: Acute exercise had no effect on the expression of UCP3L or UCP3S, but in five out of six subjects UCP2 expression decreased after exercise, although the difference was not statistically significant (P=0.11). Trained subjects had significantly reduced mRNA levels of UCP3L (P=0.028) and UCP3S (P=0. 031). VO2max expressed per kg of fat-free mass was negatively correlated with UCP3L (r=-0.61, P=0.009) and UCP3S (r=-0.52, P=0. 028). Mechanical efficiency correlated negatively with UCP3L (r=-0. 56, P=0.019), UCP3S (r=-0.47, P=0.048) and tended to correlate with UCP2 (r=-0.46, P=0.06). CONCLUSION: The lower levels of UCP3 mRNA in trained subjects and the inverse relationship of UCP3 expression and mechanical efficiency suggest that exercise training produces an adaptive physiological response in skeletal muscle improving mechanical efficiency

Iron supplements: the quick fix with long-term consequences

Co-supplementation of ferrous salts with vitamin C exacerbates oxidative stress in the gastrointestinal tract leading to ulceration in healthy individuals, exacerbation of chronic gastrointestinal inflammatory diseases and can lead to cancer. Reactive oxygen and nitrogen species (RONS) have been ascribed an important role in oxidative stress. Redox-active metal ions such as Fe(II) and Cu(I) further activate RONS and thus perpetuate their damaging effects. Ascorbic acid can exert a pro-oxidant effect by its interaction with metal ions via a number of established RONS generating systems which are reviewed here. Further studies are required to examine the detrimental effects of nutraceuticals especially in chronic inflammatory conditions which co-present with anaemia

A MIP-based biomimetic sensor for the impedimetric detection of histamine in different pH environments

The development of novel biosensors is arapidly growingfield. Substituting the biological receptor layer from the biosensor with a synthetic receptor opens the door for the development of biomimetic sensors that are chemically and physically inert, as opposed to the sensors containing biological recognition elements. Using molecularly imprinted polymers (MIPs) the specificity and affinity of biological receptors can be mimicked. In addition, a MIP-based sensor can measure in harsh environments. Histamine occurs in harsh environments in food and bodily fluids and is chosen as the target molecule for impedimetric detection. When 10nM histamine is present in pH neutral environments, the impedance increases 45% with respect to the impedance of the sensor without histamine. Specificity is tested with respect to histidine. The influence of the pH on the performance of the sensor is tested. In a pH range of pH 5-12 the MIPs are stable, although they exhibit a varying degree of protonation. The same holds true for the target molecule of which the protonation also varies with the pH of the solution. It is shown that the pH dependent degree of protonation of both the MIP and the histamine has a large impact on the bindingof histamine to the nanocavity in the MIP. Hence, the detection of histamine by a MIP-based sensor is affected by the pH of the solution. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.status: publishe

MIP-based biomimetic sensor for the electronic detection of serotonin in human blood plasma

status: publishe