Background and AimsElevated circulating concentrations of the hormone gastrin contribute to the development of gastric adenocarcinoma and types-1 and 2 gastric neuroendocrine tumors (NETs). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate proteins which in turn influence various biological processes. We hypothesised that gastrin induces the expression of specific gastric miRNAs within CCK2 receptor (CCK2R) expressing cells and that these mediate functionally important actions of gastrin.ResultsGastrin increased miR-222 expression in AGSGR cells, with maximum changes observed at 10 nM G17 for 24 h. Signalling occurred via CCK2R and the PKC and PI3K pathways. miR-222 expression was increased in the serum and gastric corpus mucosa of hypergastrinemic INS-GAS mice and hypergastrinemic patients with autoimmune atrophic gastritis and type 1 gastric NETs; it decreased in patients following treatment with the CCK2R antagonist netazepide (YF476). Gastrin-induced miR-222 overexpression resulted in reduced expression and cytoplasmic mislocalisation of p27kip1, which in turn caused actin remodelling and increased migration in AGSGR cells.Materials and MethodsmiRNA PCR arrays were used to identify changes in miRNA expression following G17 treatment of human gastric adenocarcinoma cells stably transfected with CCK2R (AGSGR). miR-222 was further investigated using primer assays and samples from hypergastrinemic mice and humans. Chemically synthesised mimics and inhibitors were used to assess cellular phenotypical changes associated with miR-222 dysregulation.ConclusionsThese data indicate a novel mechanism contributing to gastrin-associated gastric tumor development. miR-222 may also be a promising biomarker for monitoring gastrin induced premalignant changes in the stomach.
Emulsifiers are common components of processed foods consumed as part of a Western diet. Emerging in vitro cell‐line culture, mouse model and human intestinal tissue explant studies have all suggested that very low concentrations of the food emulsifier polysorbate 80 may cause bacterial translocation across the intestinal epithelium, intestinal inflammation and metabolic syndrome. This raises the possibility that dietary emulsifiers might be factors in conditions such as coronary artery disease, type 2 diabetes and Crohn's disease. The potential mechanism behind the observed effects of this emulsifier is uncertain but may be mediated via changes in the gut microbiota or by increased bacterial translocation, or both. It is also unknown whether these effects are generalisable across all emulsifiers and detergents, including perhaps the natural emulsifier lecithin or even conjugated bile acids, particularly if the latter escape reabsorption and pass through to the distal ileum or colon. A major objective of the Medical Research Council (MRC)‐funded Mechanistic Nutrition in Health (MECNUT) Emulsifier project is therefore to investigate the underlying mechanisms and effects of a range of synthetic and natural emulsifiers and detergents in vitro and in vivo, and to determine the effects of a commonly consumed emulsifier (soya lecithin) on gut and metabolic health through a controlled dietary intervention study in healthy human volunteers – the FADiets study. This report provides an overview of the relevant literature, discussing the impact of emulsifiers and other additives on intestinal and metabolic health, and gives an overview of the studies being undertaken as part of the MECNUT Emulsifier project.
The pathway recommends that acute presentations of asthma and/or rhinitis should be treated separately. Where both conditions exist, ongoing management should address the upper and lower airways. The authors recommend that this pathway is implemented locally by a multidisciplinary team (MDT) with a focus on creating networks. The MDT within these networks should work with patients to develop and agree on care plans that are age and culturally appropriate.
Effective eczema management is holistic and encompasses an assessment of severity and impact on quality of life, treatment of the inflamed epidermal skin barrier, recognition and treatment of infection and assessment and management of environmental and allergy triggers. Patient and family education which seeks to maximise understanding and concordance with treatment is also important in all children with eczema.
Objectives The provision of emergency hormonal contraception (EHC) through community pharmacies was introduced in Hambleton and Richmondshire, North Yorkshire, UK in December 2001 to contribute to the Teenage Pregnancy Strategy. The study aimed to establish how well the service is used, whether it is reaching the original target group, why people use the service and where it is accessed.Methods This was a descriptive study conducted in a rural primary care trust.Results From 1 January 2001 to 31 December 2003, there were 1412 pharmacy consultations for EHC and 1260 courses of EHC provided. General practitioner (GP) prescribing of EHC decreased but there was an overall increase in provision of EHC from pharmacies, GPs, family planning clinics, and accident and emergency departments. By December 2003, community pharmacies had become the largest provider of EHC.
ConclusionsThe supply of EHC through community pharmacies provided clients with wider choice and improved access to services, which resulted in increased overall provision of EC in this rural area. G Community pharmacies became the main point of access but did not replace other points of access.
The safety and tolerability of sumatriptan have been extensively studied. The majority of adverse events (defined as any medical event irrespective of possible causal relationship to treatment) were mild to moderate in intensity, transient and resolved spontaneously. In short-term studies, the most frequently reported adverse events were nausea, vomiting, dizziness, vertigo, malaise, fatigue, injection-site reactions, heaviness, pressure, feelings of warmth and headache. The adverse event profile was unchanged during long-term open treatment and was unaffected by frequency of treatment with sumatriptan. In 3-5% of patients, the symptoms of pressure and warmth were experienced in the chest, but extensive investigations, including ECG monitoring, have indicated that these symptoms are not normally associated with cardiac dysfunction.
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