Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

[Some practical questions on chronic stipsis treatment with prucalopride]. / Alcune domande pratiche sulla terapia della stipsi cronica con prucalopride.

Chronic constipation is a frequent pathological condition bearing relevant socioeconomic burdens, mainly due to uncertain management and unsatisfactory response to traditional laxatives. Prucalopride is a novel enterokinetic drug, that has been demonstrated to improve bowel functions and relieve a broad spectrum of digestive symptoms in patients with severe chronic constipation who had failed to respond to various traditional laxatives. In this paper we discussed the practical aspects of chronic constipation treatment, in particular focusing on some questions about the practical use of prucalopride. Prucalopride is a potent, selective, high-affinity agonist of the 5-HT4 receptors widely expressed in the gastrointestinal tract. Unlike other 5-HT4 agonists, such as cisapride and tegaserod, it is devoid of adverse cardiovascular effects. Furthermore, it is characterized by a low potential for interactions with other drugs, due to its pharmacokinetic characteristics. Prucalopride was approved, in 2009, by the European Medicines Agency for the symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief, however, there are ongoing studies to extend the use of the drug even to males.

Fiber and macrogol in the therapy of chronic constipation.

Chronic constipation is a common condition in the general population. Although the majority of affected individuals do not seek medical consultation and search for remedies for their condition in the pharmacy or herbal shops, the actual health burden caused by this condition is extremely high. Many laxatives are available, but patients are often dissatisfied with the therapies adopted, whether prescribed by a doctor or self prescribed, and this leads to further social and health burdens. All of the available guidelines promote initiating the therapy of any type of constipation by ensuring an adequate intake of dietary fiber and water. However, high amounts of insoluble vegetable fiber such as those normally contained in fruits and vegetables, can lead to a further worsening of the digestive symptoms typical of chronic constipation, such as bloating and distension and pain. Better results can be obtained with soluble fibers, such as psyllium. Among the various available laxatives, polyethylene glycol (PEG), or macrogol, is the product which has been most studied and has produced the best results with the least number of side effects. This is an inert not absorbable molecule that, diluted in water, forms an isotonic solution that prevents part of the water from being absorbed, thus increasing the volume of the intestinal contents, reducing the consistency and facilitating transport and evacuation. The combination of psyllium and PEG could combine the advantages of fiber and isotonic solutions and represent an important therapeutic option for patients suffering from chronic constipation.

[Post-infectious irritable bowel syndrome]. / Sindrome dell'Intestino Irritabile Post-infettivo.

Acute infectious gastroenteritis is the strongest known risk factor for the development of irritable bowel syndrome (IBS), one of the most common functional gastrointestinal disorders. The knowledge about the incidence and prevalence of post-infectious IBS (PI-IBS) in the general population is still limited. Risk factors have been identified in the development of PI-IBS. These include the virulence of the pathogen, younger age, female sex, the long duration of the initial illness and the presence of psychological disturbances. Histopathologic data demonstrate a low-grade mucosal inflammation in a subset of patients with IBS. Furthermore, a change in intestinal microflora could also be involved although confirmatory studies are required. The use of probiotics or non absorbable antibiotics during the acute infective episode could play a preventive role. Nonetheless, the discovery that an infective episode may trigger the development of IBS has not substantially changed the clinical management of this subset of patients compared to the classical (non infective) form of IBS. Future studies aimed at identifying specific therapies are waited.

Abdominal pain and ECG alteration: a simple diagnosis?

Acute pancreatitis is a disease initially located into the pancreas that may become a systemic disease involving organs distant from the pancreas. All organs may be involved during an acute attack of pancreatitis: lungs, kidney, heart, liver, brain. The differential is sometime difficult because acute pancreatitis may sometimes mimic an acute coronary syndrome. We report a case of a 36-year-old man who was admitted to Emergency Room for persistent epigastric pain. Serial electrocardiograms (ECG) showed signs of acute myocardial infarction. However, a coronary angiogram demonstrated no coronary artery disease, and serum troponin was undetectable. Later, serum pancreatic enzyme levels were elevated and an ultrasonography scan of the abdomen was consistent with pancreatitis. Physicians should keep in mind the possibility of an attack of pancreatitis in a patient with abdominal pain and ECG modifications who is a heavy drinker.