BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls. CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease. 相似文献
Background and Aim: Nocturnal gastro‐esophageal reflux causes heartburn and sleep disturbances impairing quality of life. Lifestyle modifications, like bed head elevation during sleep, are thought to alleviate the symptoms of gastroesophageal reflux. We tested the hypothesis that bed head elevation might decrease recumbent acid exposure compared to sleeping in a flat bed. Methods: Patients of symptomatic nocturnal reflux and documented recumbent (supine) reflux verified by esophageal pH test entered the trial. On day 1, baseline pH was measured while the patient slept on a flat bed. Then patients slept on a bed with the head end elevated by a 20‐cm block for the next 6 consecutive days from day 2 to day 7. The pH test was repeated on day 2 and day 7. Each patient acted as his own control. Results: Twenty of 24 (83.3%) patients with mean age of 36 ± 5.5 years completed the trial. The mean (± SD) supine reflux time %, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 ± 8.4 and 13.7 ± 7.2; P = 0.001, 3.8 ± 2.0 and 3.0 ± 1.6; P = 0.001, 3.3 ± 2.2 and 1.0 ± 1.2; P = 0.001, and 2.3 ± 0.6 and 1.5 ± 0.6; P = 0.04, respectively. The sleep disturbances improved in 13 (65%) patients. Conclusions: Bed head elevation reduced esophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance. 相似文献
Introduction: Cancer initiating or stem cells (CSCs) are a small population of cells in the tumor mass, which have been reported to be present in different types of cancers. CSCs usually reside within the tumor and are responsible for reoccurrence of cancer. The imprecise, inaccessible nature and increased efflux of conventional therapeutic drugs make these cells resistant to drugs. We discuss the specific markers for identification of these cells, role of CSCs in chemotherapy resistance and use of different therapeutic means to target them, including elucidation of specific cell markers, exploitation of different signaling pathways and use of nanotechnology.
Area covered: This review covers cancer stem cell signaling which are used by these cells to maintain their quiescence, stemness and resistant phenotype, distinct cell surface markers, contribution of these cells in drug resistance, inevitability to cure cancer and use of nanotechnology to overcome this hurdle.
Expert opinion: Cancer stem cells are the main culprit of our failure to cure cancer. In order to cure cancer along with other cells types in cancer, cancer stem cells need to be targeted in the tumor bed. Nanotechnology solutions can facilitate clinical translation of the therapeutics along with other emerging technologies to cure cancer. 相似文献
BACKGROUND: Therapeutic endoscopy has provided a new means of treating bleeding peptic ulcers. Additional medical therapy may enhance the therapeutic benefit. Hemostasis is highly pH dependent and is severely impaired at low pH. Proton pump inhibitors, by achieving a significantly higher inhibition of gastric acidity, may improve the therapeutic outcomes after endoscopic treatment of ulcers. PATIENT AND METHODS: We enrolled 166 patients with hemorrhage from duodenal, gastric, or stomal ulcers and signs of recent hemorrhage, as confirmed by endoscopy. Twenty-six patients had ulcers with an arterial spurt, 41 patients had active ooze, 37 had a visible vessel, and 62 patients had an adherent clot. All patients received endoscopic injection sclerotherapy using 1:10,000 adrenaline and 1% polidocanol and were randomly assigned to receive omeprazole (40 mg orally) every 12 hours for 5 days or an identical-looking placebo. The outcome measures used were recurrent bleeding, surgery, blood transfusion, and hospital stay. RESULTS: Six (7%) of 82 patients in the omeprazole group had recurrent bleeding, as compared with 18 (21%) in the placebo group (P = 0.02). Two patients in the omeprazole group and 7 patients in the placebo group needed surgery to control their bleeding (P = 0.17). One patient in the omeprazole group and 2 patients in the placebo group died (P = 0.98). Twenty-nine patients (35%) in the omeprazole group and 61 patients (73%) in the placebo group received blood transfusions (P <0.001). The average hospital stay was 4.6 +/- 1.1 days in the omeprazole group and 6.0 +/- 0.7 days in the placebo group (P <0.001). CONCLUSION: The addition of oral omeprazole to combination injection sclerotherapy decreases the rate of recurrent bleeding, reduces the need for surgery and transfusion, and shortens the hospital stay for patients with stigmata of recent hemorrhage. 相似文献