Acetylcholine has been detected in human blood. Acetylcholine receptors and acetylcholinesterase are present in erythrocyte membranes. We tested the acetylcholine and choline effects on nitric oxide metabolites (NOx), namely nitrites and nitrates, and observed if they are dependent on interactions with muscarinic receptors and acetylcholinesterase. Human erythrocyte suspensions were incubated with acetylcholine and choline in the absence or presence of 10 microM atropine or 10 microM velnacrine maleate. The nitrite and nitrate concentrations were determined by the Griess method. Acetylcholine or choline increased NOx control concentrations (P <0.001). The nitrite concentrations decreased in the presence of atropine or velnacrine maleate (P <0.03). The nitrate concentrations only decreased when velnacrine maleate was incubated with acetylcholine or choline (10 microM, P <0.03). These results demonstrated that acetylcholine and choline modulate nitric oxide metabolites on erythrocytes and this effect is mediated by interactions with erythrocyte membrane muscarinic receptors and membrane enzyme acetylcholinesterase. A hypothesis for the signal transduction mechanism has been discussed for acetylcholinesterase and muscarinic receptor (M1) participation.

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Variations in RA PAB were found across selected countries with Portugal showing the lowest proportion. GDP per capita, biologics distribution channel and consumption of MTX appear to be the best explanatory factors for these fluctuations in European countries.

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BackgroundThe access to healthcare and treatment by rheumatoid arthritis (RA) patients, particularly to biologics, differs significantly among European countries.We aimed to explore the views and experiences of Portuguese healthcare stakeholders on key barriers which limit the access to treatment, and ultimately to biologics, by RA patients and to find potential solutions (leverage points) to overcome the identified barriers.MethodsThis was a qualitative research consisting of semi-structured face-to-face interviews with key stakeholders in RA framework. Thirty four individuals from eight groups of stakeholders were interviewed: rural and urban general practitioners (GPs), rheumatologists, hospital managers, hospital pharmacists, budget holders, representatives from the Portuguese Rheumatology Society and the RA Patient Association. Interviews were conducted between May and June 2011. Conventional content analysis with research triangulation was used.ResultsThe key barriers identified were related to the accessibility to primary healthcare services, difficulties in RA diagnosis among GPs, inefficient referral to secondary healthcare and controlled process of biologics prescription in public hospitals. The leverage points identified included the improvement of epidemiological and clinical knowledge about RA in Portugal, a better understanding of the disease among patients and GPs, the clarification of biologics benefits among budget holders and a raised awareness of the current treatment guidelines. In order to further address the leverage points, the following key initiatives were proposed: optimization of RA national registry; dissemination of information on rheumatic symptoms in primary care facilities and among the general public; increase interaction between rheumatologists and GPs through clinical discussions of successfully treated patients or workshops; broader utilization of disease diagnosis and monitoring tools, such as DAS28, and implementation of hospital–based research to collect real-world data.ConclusionsMost of the key barriers limiting the access to treatment, including biologics, in RA in Portugal are upstream of rheumatology practice. Our findings suggest that future actions should be focused on the primary care level to improve referral to rheumatologists. In addition, the collection of real-world data seems essential to characterise the RA population, to improve disease management and to increase compliance with current treatment guidelines.