Background & Aims An important component of enteric inhibitory neurotransmission is mediated by a purine neurotransmitter, such as adenosine 5’-triphosphate (ATP), binding to P2Y1 receptors and activating small conductance K+ channels. In murine colon ß-nicotinamide adenine dinucleotide (ß-NAD) is released with ATP and mimics the pharmacology of inhibitory neurotransmission better than ATP. Here ß-NAD and ATP were compared as possible inhibitory neurotransmitters in human and monkey colons. Methods A small-volume superfusion assay and HPLC with fluorescence detection were used to evaluate spontaneous and nerve-evoked overflow of ß-NAD, ATP and metabolites. Postjunctional responses to nerve stimulation, ß-NAD and ATP were compared using intracellular membrane potential and force measurements. Effects of ß-NAD on smooth muscle cells (SMCs) were recorded by patch clamp. P2Y receptor transcripts and proteins were assayed by RT-PCR. Results In contrast to ATP, overflow of ß-NAD evoked by electrical field stimulation correlated with stimulation frequency and was diminished by neurotoxins, tetrodotoxin and ω-conotoxin GVIA. Inhibitory junction potentials and responses to exogenous ß-NAD, but not ATP, were blocked by P2Y receptor antagonists suramin, PPADS, MRS2179 and MRS2500. ß-NAD activated non-selective cation currents in SMCs, but failed to activate outward currents. Conclusions ß-NAD meets the criteria for a neurotransmitter better than ATP in human and monkey colons and therefore may contribute to neural regulation of colonic motility. SMCs are unlikely targets for inhibitory purine neurotransmitters because dominant responses of SMCs were activation of net inward, rather than outward, current.

Rectal sensitivity was enhanced in D-IBS patients with moderately increased mucosal mast cells, but it was attenuated in patients with markedly increased ones. This study might provide evidence for an important role of mast cells in visceral hypersensitivity.

Background and Aims: Epidemiologic studies provide evidence for a link between obesity or diabetes and the risk for colorectal cancer. However, there is a lack of information about the relationship between metabolic syndrome and colorectal adenoma. Therefore, we investigated whether metabolic syndrome is a risk factor for colorectal adenoma. Methods: We did a study for consecutive subjects who underwent colonoscopy as a screening exam at the Center for Health Promotion, Samsung Medical Center, from March 2004 to December 2005. According to the modified ATP III criteria, metabolic syndrome was diagnosed. We classified a total of 2,531 subjects into the adenoma group (n = 731) and the control group (n = 1,800), including normal colonoscopic finding, nonpolyp benign lesions, or histologically confirmed hyperplastic polyp.

Background/AimsEnvironmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia.MethodsConsensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group.ResultsTwenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added.ConclusionsThis consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Background Determination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC. Materials and Methods We analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa using beadchip array-based technology. Results We identified 621 CpG sites located in promoter regions and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. The genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. Compared to the genome-wide expression array, mRNA expression was more likely to be down-regulated in the genes demonstrating promoter hypermethylation, even though this was not statistically significant. We validated 10 CpG sites that were hypermethylated (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylation (MAEL, SFT2D3) in CRC compared to the normal mucosa in the array studies using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. Conclusions Methylation profiling based on beadchip arrays is an effective method for screening aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.

Probiotic bacteria exhibit a variety of properties, which are unique to a particular strain. Lactobacillus acidophilus-SDC 2012, 2013 are new strains isolated from Korean infants' feces. The potential utility of Lactobacillus acidophilus-SDC 2012, 2013 in irritable bowel syndrome (IBS) was studied. Forty IBS patients were randomized into a placebo (n = 20) and probiotics group (n = 20). Four weeks of treatment with L. acidophilus-SDC 2012, 2013 was associated with a reduced score for abdominal pain or discomfort compared to the baseline (P = 0.011). The percent reduction in abdominal pain or discomfort exceeded the placebo scores by more than 20% (23.8 and 0.2% for probiotics and placebo, respectively, P = 0.003). There was a significant difference in the proportion of responders between the probiotics and placebo groups (P = 0.011). There was no drop out or adverse events for either group during the study period. Lactobacillus acidophilus-SDC 2012, 2013 appeared to have a beneficial effect in patients with IBS. Further studies are warranted.

Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

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