The role of proton pump inhibitors in NSAID-associated gastropathy and upper gastrointestinal symptoms

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found with an endoscopy in 15%-30% of patients who are using NSAIDs regularly, and the annual incidence of upper gastrointestinal (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs. H2-receptor antagonists when used at standard doses are not effective at preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol effectively decreases NSAID-induced ulcers and GI complications, but issues of compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia) may limit its use. Once-daily therapy with proton pump inhibitors has been documented to significantly decrease the development of NSAID-associated ulcers in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and reduce upper GI symptoms in NSAID users.     

Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies

OBJECTIVES: The aim of this study was to assess the development of erosive esophagitis, the development of gastroesophageal reflux disease (GERD) symptoms in patients without prior symptomatic or endoscopic GERD, and the worsening of GERD symptoms in patients with prior symptomatic GERD in a post hoc analysis of eight double-blind prospective trials of Helicobacter pylori (H. pylori) therapy in 1165 patients. METHODS: Patients with active or past duodenal ulcer and without baseline erosive esophagitis had end of study endoscopies 4-30 wk after completion of therapy. A total of 533 patients had heartburn and regurgitation scores assessed at baseline and 4 wk after end of therapy, and were divided into two groups: 1) no prior GERD symptoms (N = 127) and 2) prior GERD symptoms (N = 406). H. pylori was assessed at baseline and > or = 4 wk after therapy by rapid urease test, histology, and culture. RESULTS: Erosive esophagitis developed in 24 (4%) of 621 patients with cure versus 14 (3%) of 544 with persistent H. pylori (OR = 1.52, 95% CI = 0.78-2.97). In the longest study (28-30-wk follow-up), esophagitis developed in two (7%) of 28 patients with cure versus five (7%) of 76 with persistent infection. New GERD symptoms developed in 13 (14%) of 92 patients with cure versus seven (20%) of 35 with persistent infection (OR = 0.66,95% CI = 0.24-1.82). GERD worsened in 20 (7%) of 269 with cure vs 20 (15%) of 137 with persistent H. pylori (OR = 0.47, 95% CI = 0.24-0.91; p = 0.02). CONCLUSIONS: Our results do not support the hypothesis that H. pylori eradication in patients with duodenal ulcer disease leads to the development of erosive esophagitis, the development of new symptomatic GERD, or worsening of symptoms in patients with pre-existing GERD.     

Microsatellite Analysis of Sporadic Flat and Depressed Lesions of the Colon

Prior studies of molecular and genetic derangements in flat and depressed lesions of the colon have revealed lower frequencies in a number of markers commonly present in exophytic lesions. These and other differences suggest that flat lesions are driven by alternative pathways. We reviewed a database of patients who had undergone endoscopic mucosal resection (EMR) for flat and depressed lesions at the University of Chicago from January 2001 to April 2003. Formalin-fixed and paraffin-embedded colonic samples were retrieved from the tissue bank, and five standardized mononucleotide and dinucleotide microsatellite regions were analyzed for instability (MSI) using fluorescently labeled forward primers in nonmultiplex reactions. Sixteen patients were identified with flat or depressed lesions who had adequate tissue specimens available for MSI analysis. Of these specimens, eight were tubular adenomas, three were tubulovillous adenomas, and five were carcinomas in situ. Four of the lesions were microsatellite unstable, each at a single locus, and one lesion showed probable instability at a second locus. Eleven lesions were microsatellite stable. Aberrations in DNA repair mechanisms do not appear to significantly contribute to the molecular derangements underlying sporadic flat or depressed colonic lesions. The molecular bases that underlie the aggressive behavior of sporadic flat and depressed lesions remain to be determined, and further investigation is warranted.     

Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT_1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT_1A receptor-mutant mice. These animals lack functional 5-HT_1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT_1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT_1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.     

Increasing homogeneity in global food supplies and the implications for food security

The narrowing of diversity in crop species contributing to the world’s food supplies has been considered a potential threat to food security. However, changes in this diversity have not been quantified globally. We assess trends over the past 50 y in the richness, abundance, and composition of crop species in national food supplies worldwide. Over this period, national per capita food supplies expanded in total quantities of food calories, protein, fat, and weight, with increased proportions of those quantities sourcing from energy-dense foods. At the same time the number of measured crop commodities contributing to national food supplies increased, the relative contribution of these commodities within these supplies became more even, and the dominance of the most significant commodities decreased. As a consequence, national food supplies worldwide became more similar in composition, correlated particularly with an increased supply of a number of globally important cereal and oil crops, and a decline of other cereal, oil, and starchy root species. The increase in homogeneity worldwide portends the establishment of a global standard food supply, which is relatively species-rich in regard to measured crops at the national level, but species-poor globally. These changes in food supplies heighten interdependence among countries in regard to availability and access to these food sources and the genetic resources supporting their production, and give further urgency to nutrition development priorities aimed at bolstering food security.A shared axiom of ecology and nutrition is that, within certain ranges, diversity enhances the health and function of complex biological systems. Species diversity has been shown to stimulate productivity, stability, ecosystem services, and resilience in natural (1–5) and in agricultural ecosystems (6–13). Likewise, variation in food species contributing to diet has been associated with nutritional adequacy (14–17) and food security (18).The development of sedentary agricultural societies and further rise of modern agriculture is generally considered to have led to a decline in the total number of plant species upon which humans depend for food (19, 20), particularly the wild, semidomesticated, and cultivated vegetables and fruits, spices, and other food plants that supplemented staple crops with the provision of micronutrients and that bolstered food security historically during crop failures (21). Harlan (20) warned that

most of the food for mankind comes from a small number of crops and the total number is decreasing steadily. In the United States in the past 40 years, many vegetables and fruits have disappeared from the diet, and the trend is going on all over the world. More and more people will be fed by fewer and fewer crops.

More recent analyses of dietary transition in developing countries in association with globalization have noted increases in the diversity of plants contributing to diets locally, along with a Westernization transition in preference of energy-dense foods (i.e., animal products, plant oils, and sugars) over cereals, pulses, and vegetables, and of particular major crop plants within these food categories over traditional crops (22, 23). The impact of such changes on overall crop diversity worldwide has not been comprehensively documented, although recent changes in varietal and allelic level diversity of some crops have been investigated (24–26). Given the potential food security implications of narrowing of the diversity of crop species both in production systems and in food supplies, an assessment of the global state of crop plant species diversity is warranted.Here we examine changes in the diversity of the portfolio of crop species upon which humans primarily depend for food security in regard to calories, protein, fat, and food weight. Using national per capita food supply data published by the Food and Agriculture Organization (FAO) of the United Nations, we analyzed trends in the richness, abundance, and composition of measured crop commodities in the food supplies of 152 countries comprising 98% of the world’s population from 1961 to 2009.