The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis,which depends upon the balance between mucosal injury by destructive factors and healing via protective factors.The persistence of n...The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis,which depends upon the balance between mucosal injury by destructive factors and healing via protective factors.The persistence of noxious agents such as acid,pepsin,nonsteroidal anti-inflammatory drugs,or Helicobacter pylori breaks down the mucosal barrier and injury occurs.Depending upon the size and site of the wound,it is healed by complex and overlapping processes involving membrane resealing,cell spreading,purse-string contraction,restitution,differentiation,angiogenesis,and vasculogenesis,each modulated by extracellular regulators.Unfortunately,the gut does not always heal,leading to such pathology as peptic ulcers or inflammatory bowel disease.Currently available therapeutics such as proton pump inhibitors,histamine-2 receptor antagonists,sucralfate,5-aminosalicylate,antibiotics,corticosteroids,and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract.More recent studies have focused on improving mucosal defense or directly promoting mucosal repair.Many investigations have sought to enhance mucosal defense by stimulating mucus secretion,mucosal blood flow,or tight junction function.Conversely,new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin,talin,Ehm^(2),filamin-a,gelsolin,and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase.This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.展开更多
A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once...A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.展开更多
文摘The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis,which depends upon the balance between mucosal injury by destructive factors and healing via protective factors.The persistence of noxious agents such as acid,pepsin,nonsteroidal anti-inflammatory drugs,or Helicobacter pylori breaks down the mucosal barrier and injury occurs.Depending upon the size and site of the wound,it is healed by complex and overlapping processes involving membrane resealing,cell spreading,purse-string contraction,restitution,differentiation,angiogenesis,and vasculogenesis,each modulated by extracellular regulators.Unfortunately,the gut does not always heal,leading to such pathology as peptic ulcers or inflammatory bowel disease.Currently available therapeutics such as proton pump inhibitors,histamine-2 receptor antagonists,sucralfate,5-aminosalicylate,antibiotics,corticosteroids,and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract.More recent studies have focused on improving mucosal defense or directly promoting mucosal repair.Many investigations have sought to enhance mucosal defense by stimulating mucus secretion,mucosal blood flow,or tight junction function.Conversely,new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin,talin,Ehm^(2),filamin-a,gelsolin,and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase.This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
文摘A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.