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    ABSTRACT: Abdominal pain is one of the most frequent reasons for consulting a doctor. Despite it being a common clinical presentation, abdominal pain remains a difficult entity to treat. This is a result of multiple factors including time course (i.e., acute vs. chronic), etiology (e.g., inflammatory vs. post-inflammatory), and stimulus (i.e., mechanical vs. chemical). About 10% of the population suffer from chronic visceral pain in the form of irritable bowel syndrome (IBS), many of which go undiagnosed. They are hypersensitive to contraction and distension of the gut (Barbara et al., 2011; Keszthelyi et al., 2012), but the pathophysiology of pain is poorly understood. While the intestinal epithelium is a site of high metabolic activity, including digestion/absorption, secretion, hormone release, and immune interactions, it is generally not viewed as a site of pain modulation. However, there are numerous factors at the level of the epithelium capable of modulating pain. This article will highlight the potential role of these factors in nociceptive signaling to identify new therapeutic targets.
    Full-text · Article · Apr 2014 · Frontiers in Pharmacology
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    ABSTRACT: The growth of human tumor cells transplanted into immunodeficient mice is frequently studied to gain understanding about the way potential drug treatments interfere with growth in vivo. A wide range of methods is available for learning about specific aspects of tumor cell behavior, for example, cells may be administered to follow their ability to grow close to the site of injection which may be at a generic site or one specific to that type of tumor. Some models of metastasis follow the appearance of a tumor mass after intravascular administration of tumor cells; others score remote growth after removal of a primary tumor implanted subcutaneously. Assessing metastatic growth may increasingly rely on serial observation of tumor cell numbers as seen by whole-body imaging, but the sensitivity of these methods is poor in terms of the minimum number of cells detectable, and histological follow-up to establish tumor cell numbers can be confounded by variable expression or even silencing of reporter genes. Here we describe how fluorescence in situ hybridization (FISH) using commercially available probes can very easily be used to detect even single metastatic tumor cells in mouse models, using routinely fixed and processed tissue samples, and without the tumor cell lines needing to express engineered reporter genes. The FISH protocol can be combined with other standard histological protocols to study the behavior of tumor cells and adjacent host cells to improve our understanding of tumor-stroma interactions, and is also useful for simultaneous demonstration of the cell of origin and phenotype of cells used in regenerative medicine-based applications.
    No preview · Article · Jan 2014 · Methods in molecular biology (Clifton, N.J.)
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    ABSTRACT: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.
    No preview · Article · Nov 2013 · Alimentary Pharmacology & Therapeutics
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