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IntroductionDrotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon.MethodsColon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1 µM tetrodotoxin) and (2) contractility induced by 10–5 M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1 mM Nω-nitro-L-arginine and 10 µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin.ResultsCompared with the vehicle, drotaverine and paracetamol (10−9–10−5 M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10−7–10−5 M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10−4 M) and hyoscine butylbromide (10−7–10−5 M) was not different from hyoscine butylbromide alone (10−7–10−5 M). At higher concentrations (10−3M–3*10−3 M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10–7 M was concentration-dependently enhanced by drotaverine (10−6M–10−5M).DiscussionPeppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by microvascular damage and fibrosis. Mortality in patients with SSc has significantly decreased. Consequently, patients with SSc have longer life expectancy, and health-related quality of life (HrQoL) has become more relevant in the comprehensive management of the disease.Objective To evaluate the impact between gastrointestinal (GI) symptom burden and psychological well-being on HrQoL in patients with SSc.Design Nested cross-sectional study conducted between January and July 2022.Participants A single-centre cohort of 166 patients with SSc, including 103 (55%) with limited cutaneous SSc, 43 (24%) with diffuse SSc and 37 (21%) with sine-sclerosis SSc.Main measures GI symptom burden was assessed using the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract 2.0 (UCLA SCTC GIT 2.0) questionnaire, psychological well-being was measured with the Hospital Anxiety and Depression Scale (HADS), and HrQoL was evaluated using the Short Form 36 (SF-36) questionnaire. Demographic, clinical and immunological data were collected from a prospectively maintained database.Key results Patients with moderate to severe GI symptoms (UCLA SCTC GIT 2.0 score >0.5, n=95, 57%) reported decreased HrQoL in all subdomains except vitality by SF-36, and higher anxiety and depression scores by HADS (all p