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- Jansson, Emmelie A, et al.
(author)
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Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate
- 2007
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 42:4, s. 510-518
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Journal article (peer-reviewed)abstract
- Nitrate is abundant in our diet with particularly high levels in many vegetables. Ingested nitrate is concentrated in saliva and reduced to nitrite by bacteria in the oral cavity. We recently reported that application of nitrite-containing saliva to the gastric mucosa increases superficial blood flow and mucus generation via acid-catalyzed formation of bioactive nitrogen oxides including nitric oxide. Here we studied if dietary supplementation with nitrate would protect against gastric damage caused by a nonsteroidal anti-inflammatory drug. Rats received sodium nitrate in the drinking water for 1 week in daily doses of 0.1 or 1 mmol kg− 1. Control rats received 1 mmol kg− 1 sodium chloride. Diclofenac (30 mg kg− 1) was then given orally and the animals were examined 4 h later. In separate experiments we studied the effects of dietary nitrate on intragastric NO levels and mucus formation. Luminal levels of NO gas were greatly increased in nitrate-fed animals. The thickness of the mucus layer increased after nitrate supplementation and gene expression of MUC6 was upregulated in the gastric mucosa. Nitrate pretreatment dose dependently and potently reduced diclofenac-induced gastric lesions. Inflammatory activity was reduced in the rats receiving nitrate as indicated by lower mucosal myeloperoxidase activity and expression of inducible NO synthase. We conclude that dietary nitrate protects against diclofenac-induced gastric ulcers likely via enhanced nitrite-dependent intragastric NO formation and concomitant stimulation of mucus formation. Future studies will reveal if a diet rich in nitrate can offer an additional nutritional approach to preventing and treating peptic ulcer disease.
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- Reinders, Claudia I
(author)
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Nitric oxide : a surrogate marker of bowel inflammation
- 2005
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Doctoral thesis (other academic/artistic)abstract
- The gas nitric oxide (NO) is a pluripotent biological messenger involved in numerous physiological and pathological processes in the gastrointestinal (GI) tract. In the intestinal mucosa NO is synthesized from the amino acid L-arginine via a reaction catalyzed by NO synthase (NOS). During inflammation, mucosal NO generation is increased and NO gas is released in the gut lumen. We have developed a procedure for direct measurement of gaseous NO in the GI tract. Employing this procedure, the present thesis was designed to evaluate further the potential usefulness of measurements of rectal levels of NO in diagnosing inflammatory bowel disease (IBD) and monitoring the response of this disease to treatment. Altogether, 89 patients with IBD, 39 with irritable bowel syndrome (IBS) and 28 with collagenous colitis (CC), were examined. Rectal NO levels were measured employing a tonometric method using a silicon catheter equipped with an inflatable balloon and compared to clinical indices of disease activity. We also characterized the effect of systemic inhibition of NOS (by LNMMA) on rectal levels of NO in patients with collagenous colitis to further pinpoint the source of rectal NO. Finally, we investigated the possibility that commensal gut bacteria can produce NO. In healthy subjects rectal levels of NO were low and varied little with time. Slightly and highly elevated levels were observed in patients with IBS and IBD respectively. This parameter demonstrated a sensitivity of 95 % and specificity of 91 % in discriminating between IBS and active IBD. Rectal levels of NO were correlated to disease activity in patients with IBD or CC and were reduced markedly in IBD patients who responded to treatment. Surprisingly, rectal levels of NO were not correlated to fecal calprotectin levels, another marker of IBD. Intravenous administration of L-NMMA reduced rectal NO levels in only half of the patients with CC examined, despite clear evidence of effective systemic inhibition of NOS. This could indicate the existence of alternative, NOS-independent sources of intestinal NO in this disorder. Human feces and certain isolated strains of bacteria were capable of generating NO in the presence of nitrate andlor nitrite in vitro. In addition, NO generation was observed in the gut lumen of conventional rats, but not of germ-free rats or rats colonized by lactobacilli. Thus, bacteria can be a significant source of NO in the gut. We conclude that measurements of rectal levels of NO could be clinically useful as a rapid and minimally invasive procedure for discriminating between active bowel disease and IBS, as well as a possible source of useful supplemental information when monitoring the treatment of patients with IBD. Future studies will reveal the biological significance of NO generation by GI bacteria with regards to the regulation of GI integrity and the clinical usefulness of fecal calprotectin and rectal NO as surrogate markers for bowel inflammation, as well as the exact role played by these substances in the pathogenesis of this disorder.
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- Van Doesum, Niels J., et al.
(author)
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Social mindfulness and prosociality vary across the globe
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:35
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Journal article (peer-reviewed)abstract
- Humans are social animals, but not everyone will be mindful of others to the same extent. Individual differences have been found, but would social mindfulness also be shaped by one's location in the world? Expecting cross-national differences to exist, we examined if and how social mindfulness differs across countries. At little to no material cost, social mindfulness typically entails small acts of attention or kindness. Even though fairly common, such low-cost cooperation has received little empirical attention. Measuring social mindfulness across 31 samples from industrialized countries and regions (n = 8,354), we found considerable variation. Among selected country-level variables, greater social mindfulness was most strongly associated with countries' better general performance on environmental protection. Together, our findings contribute to the literature on prosociality by targeting the kind of everyday cooperation that is more focused on communicating benevolence than on providing material benefits.
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