Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease

Background Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. Methods In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. Results The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P = 0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. Conclusions We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group

Un contributo alla consapevolezza nelle scelte alimentari, nell'ottica dell'educazione alla salute

Viene descritto un progetto di tirocinio realizzato all\u2019interno della SSIS per la formazione degli insegnanti. Il tema scelto riguarda l\u2019alimentazione, la cui educazione \ue8 indispensabile per i giovanissimi sempre pi\uf9 soggetti a mode importate e dannose per la salute. Vengono anche descritti esempi di lavoro in classe

Insecticide Control of Drosophila suzukii in Commercial Sweet Cherry Crops under Cladding

Drosophila suzukii Matsumura is a damaging invasive pest of sweet cherry. Using a series of laboratory leaf contact assays, semi-field, and orchard spray programs we aimed to determine the impact of insecticide programs on D. suzukii adult mortality and oviposition in cladding-protected sweet cherry crops. Tests included assessing adult D. suzukii mortality after contact with leaves sprayed either one or two weeks previously and emergence of adults from fruits. Spinosad, lambda-cyhalothrin, acetamiprid, lime, pyrethrin, deltamethrin, and cyantraniliprole all reduced fruit damage up to day 7 after application. Of these active ingredients, only spinosad, lambda-cyhalothrin, and cyantraniliprole gave satisfactory control up to 14 days. There was no significant difference in D. suzukii mortality when exposed to leaves treated either one or two weeks previously with an application of either spinosad, cyantraniliprole, or lambda-cyhalothrin; however, mortality was significantly higher than D. suzukii in contact with untreated leaves. In eight commercial orchards, fortnightly spray applications including spinosad, cyantraniliprole, and lambda-cyhalothrin gave effective control of D. suzukii until harvest with very few damaged fruits. These experiments demonstrate that currently approved plant protection products, applied to sweet cherry under protection, give at least two weeks protection from D. suzukii

Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease

Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P&lt;0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P&lt;0.001, and P&lt;0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo