NOD-like receptors in the human upper airways: a potential role in nasal polyposis.

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. METHODS: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. RESULTS: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. CONCLUSIONS: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.

Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?

BACKGROUND: Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. AIM OF THE STUDY: To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. METHODS: The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. RESULTS: Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. CONCLUSION: Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease.

GLP-1 inhibits gastric emptying of water but does not influence plasma.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) has been shown to inhibit gastric emptying of a caloric load but the effect on a non-caloric load is unknown. METHODS: Seven healthy men were studied after an over-night fast. Thirty min before the intake of 330 ml radioactively labeled water either GLP-1 (0.75 pmol/kg/min) or saline was administered intravenously and continued for 75 min. Scintigraphic gastric emptying was performed for 45 min and plasma samples were obtained for analysis of vasopressin, sodium, osmolality, GLP-1, insulin, and glucose. In addition, electric field stimulation of human gastric muscle strips was done. RESULTS: The median (range) percent water retained in the stomach, 45 min after intake of water, was 96% (68%-98%) and 12% (2%-42%) (P = 0.02) during infusion of GLP-1 and saline, respectively. Additionally, GLP-1 did not affect basal tone or contractile response of gastric muscle strips to electric field stimulation or acetylcholine (ACh). There was no change in plasma concentrations of vasopressin, sodium, or plasma osmolality during GLP-1 compared to saline infusion. CONCLUSION: GLP-1 has a profound inhibitory effect on the gastric emptying of water in man, but no short-term effect on water homeostasis. No effect was seen on contractility of gastric muscle strips suggesting an indirect action on gastric emptying.

Gastric emptying: comparison of scintigraphic, polyethylene glycol dilution, and paracetamol tracer assessment techniques.

BACKGROUND: The method of choice for studying gastric emptying is dependent on several factors. The aim of the present study was to assess the concordance between solid gastric emptying, using a scintigraphic technique as gold standard, and gastric emptying as measured with parcetamol tracer and polyethylene glycol (PEG) dilution. METHODS: Two groups of seven male volunteers with similar ages and weights were studied, one for scintigraphic (310-kcal omelette with 12-15 MBq 99mTc-labeled macroaggregated albumin) and paracetamol (1.5 g dissolved in water and administered concomitantly with the omelette) and one for the marker dilution study (PEG 4000 dissolved in a 310-kcal meal). RESULTS: The gastric half-emptying time (T50) was shorter in the PEG study than in the scintigraphic test (47.5 (37.5-62) versus 68.1 (43.6-89.4), median (range) (P < 0.05), respectively), whereas there was no significant difference between the T50 for gastric emptying as assessed with the scintigraphic and paracetamol tracer methods. No difference in gastric emptying rate using PEG dilution or paracetamol tracer was obtained. CONCLUSIONS: In summary, this study shows that scintigraphic, paracetamol tracer, and PEG dilution methods can all be used to assess gastric emptying. The use of the paracetamol tracer technique offers a relatively inexpensive technique that yields a good approximation of gastric emptying as verified by the scintigraphic emptying of a solid meal.

GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans.

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 +/- 2.5 yr, body mass index 24.1 +/- 0.9 (means +/- SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol. kg(-1). min(-1)) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3-103.6 min vs. saline: 19. 5, range 10.2-43.4 min) and emptying rate (GLP-1: 0.34, range 0.06-0. 56 %/min vs. saline: 0.84, range 0.54-1.33 %/min; P < 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P < 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline (P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline (P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.