No abstract

1 Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl-D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator eects in endothelium-denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might in¯uence chemical stability and duration of vascular action of S-nitrosothiols. 2 Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a speci®c Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was con®rmed by electrochemical detection at 378C. 3 Bolus injections of SNAP (10 ml; 10 78 ± 10 73 M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400 ± 500 g), caused concentration-dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium-intact vessels but failed to recover to pre-injection pressures at moderate and high concentrations (10 76 ± 10 73 M) in those denuded of endothelium. This sustained eect (41 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. 4 We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium-denuded vessels; subsequent slow decomposition within the tissue generates sucient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage.

Aim Our aim was to compare the efficacy and tolerability of loperamide and racecadotril in elderly patients with acute diarrhea.

1 S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet eects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the eects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. 2 The eects of GSNO and RIG200 in collagen (2.5 mg ml 71 )-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was signi®cantly more potent (IC 50 =2.0 mM for GSNO and 0.8 mM for RIG200; P=0.04). 3 Neither compound inhibited aggregation in whole blood, even at concentrations of 100 mM. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (52.5 mM), signi®cantly reduced their inhibitory eects on platelets. 4 Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of eect of Snitrosothiols on platelets in whole blood. 5 These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents.

Background: The aim of this study was to determine the occurrence of gluten sensitivity (GS) in a group of allergic patients and to assess the efficacy of a gluten-free diet (GFD) on the improvement of the symptomatology in those who were diagnosed with GS. Methods: 262 unrelated allergic patients with gastrointestinal symptoms of obscure origin were tested for GS condition by biopsy. All patients were also genotyped for the typical celiac DQ2 and DQ8 molecules and investigated for several hematological parameters such as antigliadin and antiendomysial antibodies. Patients displaying mucosal lesions were invited to follow a GFD. Results: Seventy-seven of the 262 allergic patients were positive to mucosal lesions, but negative to the antiAGA, antiEMA and to DQ2 and DQ8 molecules. We found, instead, a prevalence of the DQA1*05 allele, whereas anemia of inflammatory origin represented the predominant complaint in our subjects. The positive patients, who, after the GS diagnosis, followed a GFD, exhibited control of symptoms as well as stabilization of the hematological parameters even if allergic manifestations were not abated. Conclusions: A nonceliac gluten-sensitive enteropathy (NCGSE) commonly occurs in allergic patients. Based on the high prevalence of NCGSE in allergy, it is recommended that biopsy should be part of the routine investigation of allergic disease to offer the benefits of treatment with a GFD to the patients.