• pressure sensor
• implants
• biomedical electrodes
• biomedical electronics
• wireless sensor
• flexible electronics

• Animals
• Colon
• Prostheses and Implants
• Electrodes
• Electric Impedance
• Catheters

• IK6 RX003843 RRD VA
• OT2 OD023873 NIH HHS
• OT2 OD024899 NIH HHS

• children
• constipation
• defecation
• dyssynergia
• treatment

• IBS-C
• chronic constipation
• diagnosis
• epidemiology
• investigation
• pathophysiology

• Colon
• Drug delivery
• Fluid dynamics
• Fluid-structure interactions
• Large intestine
• Mathematical modelling
• Peristalsis
• Proximal colon
• Smoothed Particle Hydrodynamics (SPH)

• Colonic dysmotility
• Constipation
• High-amplitude propulsive contractions
• High-resolution colonic manometry
• Low-amplitude propagated contractions

• CMMC
• colonic motility
• germ-free mice
• serotonin
• short-chain fatty acids

• children
• colonic manometry
• constipation
• motility

• Chromogranin A
• colon
• endocrine cells
• immunohistochemistry
• morphometry
• rectum

Inflammatory bowel disease (IBD) is a chronic recurrent condition whose etiology is unknown, and it includes ulcerative colitis, Crohn’s disease, and microscopic colitis. These three diseases differ in clinical manifestations, courses, and prognoses. IBD reduces the patients’ quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal (GI) neuroendocrine peptides/amines (NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover, the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD, and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin, the neuropeptide Y family, and substance P are proinflammatory, while the chromogranin/secretogranin family, vasoactive intestinal peptide, somatostatin, and ghrelin are anti-inflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD, and are candidate targets for treatments of this disease.

• Enteric nervous system
• Enteroendocrine cells
• Immune cells
• Inflammatory bowel disease
• Musashi-1
• Neurogenin 3
• Stem cells

• Amines/immunology
• Animals
• Chromogranins/immunology
• Chromogranins/metabolism
• Disease Models, Animal
• Gastrointestinal Microbiome
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/metabolism
• Ghrelin/immunology
• Ghrelin/metabolism
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/epidemiology
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/therapy
• Neuroendocrine Cells/immunology
• Neuroendocrine Cells/metabolism
• Neuropeptide Y/antagonists & inhibitors
• Neuropeptide Y/immunology
• Neuropeptide Y/metabolism
• Neurosecretory Systems/cytology
• Neurosecretory Systems/immunology
• Prevalence
• Quality of Life
• Recurrence
• Serotonin/immunology
• Serotonin/metabolism
• Serotonin Antagonists/therapeutic use
• Somatostatin/immunology
• Somatostatin/metabolism
• Substance P/antagonists & inhibitors
• Substance P/immunology
• Substance P/metabolism
• Vasoactive Intestinal Peptide/immunology
• Vasoactive Intestinal Peptide/metabolism

The present study aimed to determine whether there is an association between abnormalities in enteroendocrine cells in dextran sulfate sodium (DSS)-induced colitis and the clonogenic and/or proliferative activities of stem cells. A total of 48 male Wistar rats were divided into four groups. Animals in the control group were provided with normal drinking water, whereas DSS colitis was induced in the remaining three groups. The rats with DSS-induced colitis were randomized into the following three groups: i) DSS group, which received 0.5 ml 0.5% carboxymethyl cellulose (CMC; vehicle); ii) DSS-G group, which was treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide at 20 mg/kg body weight in 0.5% CMC; and iii) DSS-Q group, which was treated with dehydroxymethylepoxyquinomicin at 15 mg/kg body weight in 0.5% CMC. Treatments were administered intraperitoneally twice daily for 5 days in all groups. Subsequently, tissue samples from the colon were stained with hematoxylin-eosin, or immunostained for chromogranin A (CgA), Musashi 1 (Msi1), Math-1, neurogenin 3 (Neurog3) and neurogenic differentiation D1 (NeuroD1). The densities of CgA, Msi1-, Math-1-, Neurog3- and NeuroD1-immunoreactive cells were determined. DTCM-G, and DHMEQ ameliorated the inflammation in DSS-induced colitis. The density of CgA-, Neurog3- and NeuroD1-immunoreactive cells was significantly higher in the DSS group compared with in the control group, and the density of CgA cells was correlated with the densities of Neurog3- and NeuroD1-immunoreactive cells. There were no significant differences in the densities of Msi1- and Math-1-immunoreactive cells among the four experimental groups. The elevated densities of enteroendocrine cells detected in DSS-induced colitis may be due to the increased differentiation of early enteroendocrine progenitors during secretory lineage. It is probable that the DSS-induced inflammatory processes trigger certain signaling pathways, which control differentiation of the stem-cell secretory lineage into mature enteroendocrine cells.

Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5–230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4–5 cm apart. Synchronized haustral pressure waves, covering 3–5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3–6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal.

Approximately 3.6 million individuals suffer from inflammatory bowel disease (IBD) in the western world, with an annual global incidence rate of 3–20 cases/100,000 individuals. The etiology of IBD is unknown, and the currently available treatment options are not satifactory for long-term treatment. Patients with inflammatory bowel disease present with abnormalities in multiple intestinal endocrine cell types, and a number of studies have suggested that interactions between gut hormones and immune cells may serve a pivotal role in the pathophysiology of IBD. The aim of the present study was to investigate alterations in colonic endocrine cells in a rat model of IBD. A total of 30 male Wistar rats were divided into control and trinitrobenzene sulfonic acid (TNBS)-induced colitis groups. Colonoscopies were performed in the control and TNBS groups at day 3 following the induction of colitis, and colonic tissues were collected from all animals. Colonic endocrine and immune cells in the obtained tissue samples were immunostained and their densities were quantified. The densities of chromogranin A, peptide YY, and pancreatic polypeptide-producing cells were significantly lower in the TNBS group compared with the control group, whereas the densities of serotonin, oxyntomodulin, and somatostatin-producing cells were significantly higher in the TNBS group. The densities of mucosal leukocytes, B/T-lymphocytes, T-lymphocytes, B-lymphocytes, macrophages/monocytes and mast cells were significantly higher in the TNBS group compared with the controls, and these differences were strongly correlated with alterations in all endocrine cell types. In conclusion, the results suggest the presence of interactions between intestinal hormones and immune cells.

Patients with inflammatory bowel disease (IBD), as well as animal models of human IBD have abnormal enteroendocrine cells. The present study aimed to identify the possible mechanisms underlying these abnormalities. For this purpose, 40 male Wistar rats were divided into 4 groups as follows: the control group, the group with trinitrobenzene sulfonic acid (TNBS)-induced colitis with no treatment (TNBS group), the group with TNBS-induced colitis treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G; an activator protein-1 inhibitor) (DTCM-G group), and the group with TNBS-induced colitis treated with dehydroxymethylepoxyquinomicin (DHMEQ; a nuclear factor-κB inhibitor) treatment (DHMEQ group). Three days following the administration of TNBS, the rats were treated as follows: those in the control and TNBS groups received 0.5 ml of the vehicle [0.5% carboxymethyl cellulose (CMC)], those in the DTCM-G group received DTCM-G at 20 mg/kg body weight in 0.5% CMC, and those in the DHMEQ group received DHMEQ at 15 mg/kg body weight in 0.5% CMC. All injections were administered intraperitoneally twice daily for 5 days. The rats were then sacrificed, and tissue samples were taken from the colon. The tissue sections were stained with hemotoxylin-eosin and immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP), somatostatin, Musashi1 (Msi1), Math1, Neurogenin3 (Neurog3) and NeuroD1. The staining was quantified using image analysis software. The densities of CgA-, PYY-, PP-, Msi1-, Neurog3- and NeuroD1-positive cells were significantly lower in the TNBS group than those in the control group, while those of serotonin-, oxyntomodulin- and somatostatin-positive cells were significantly higher in the TNBS group than those in the control group. Treatment with either DTCM-G or DHMEQ restored the densities of enteroendocrine cells, stem cells and their progenitors to normal levels. It was thus concluded that the abnormalities in enteroendocrine cells and stem cells and their differentiation progenitors may be caused by certain signaling substances produced under inflammatory processes, resulting in changes in hormone expression in enteroendocrine cells. These substances may also interfere with the colonogenic activity and the differentiation of the stem-cell secretory lineage into mature enteroendocrine cells.

• chromogranin A
• genes
• low-grade inflammation
• microbiota
• peptide YY
• somatostatin
• stem cell

• Crohn's disease
• Inflammatory bowel disease
• Motility
• Secretion
• Ulcerative colitis

• Animals
• Gastrointestinal Hormones/metabolism
• Humans
• Immune System/metabolism
• Inflammatory Bowel Diseases/metabolism
• Inflammatory Bowel Diseases/physiopathology
• Neurons/metabolism
• Neuropeptide Y/metabolism
• Pancreatic Polypeptide/metabolism

• Independent component analysis
• Normal transit constipation
• Phase space reconstruction
• Slow transit constipation
• Wireless capsule

The colonic migrating motor complex (CMMC) is a critical neurally mediated rhythmic propulsive contraction observed in the large intestine of many mammals. It seems to be equivalent to the high amplitude propagating contractions (HAPCs) in humans. This review focuses on the probable neural mechanisms involved in producing the CMMC or HAPC, their likely dependence on mucosal and neuronal serotonin and pacemaker insterstitial cells of Cajal networks and how intrinsic neural reflexes affect them. Discussed is the possibility that myenteric 5-hydroxytryptamine (5-HT) neurons are not only involved in tonic inhibition of the colon, but are also involved in generating the CMMC and modulation of the entire enteric nervous system, including coupling motility to secretion and blood flow. Mucosal 5-HT appears to be important for the initiation and effective propagation of CMMCs, although this mechanism is a longstanding controversy since the 1950s, which we will address. We argue that the slow apparent propagation of the CMMC/HAPC down the colon is unlikely to result from a slowly conducting wave front of neural activity, but more likely because of an interaction between ascending excitatory and descending (serotonergic) inhibitory neural pathways interacting both within the myenteric plexus and at the level of the muscle. That is, CMMC/HAPC propagation appears to be similar to esophageal peristalsis. The suppression of inhibitory (neuronal nitric oxide synthase) motor neurons and mucosal 5-HT release by an upregulation of prostaglandins has important implications in a number of gastrointestinal disorders, especially slow transit constipation.

• 5-HT neurons
• Colon
• Colonic Motor complex
• Mucosa
• Occult reflexes

Management of chronic constipation with refractory symptoms can be challenging. Although new drugs and behavioral treatments have improved outcome, when they fail, there is little guidance on what to do next. At this juncture, typically most doctors may refer for surgical intervention although total colectomy is associated with morbidity including complications such as recurrent bacterial overgrowth. Recently, colonic manometry with sensory/tone/compliance assessment with a barostat study has been shown to be useful. Technical challenges aside, adequate preparation, and appropriate equipment and knowledge of colonic physiology are keys for a successful procedure. The test itself appears to be safe with little complications. Currently, colonic manometry is usually performed with a 6–8 solid state or water-perfused sensor probe, although high-resolution fiber-optic colonic manometry with better spatiotemporal resolutions may become available in the near future. For a test that has evolved over 3 decades, normal physiology and abnormal findings for common phenotypes of chronic constipation, especially slow transit constipation, have been well characterized only recently largely through the advent of prolonged 24-hour ambulatory colonic manometry studies. Even though the test has been largely restricted to specialized laboratories at the moment, emerging new technologies and indications may facilitate its wider use in the near future.

• Barostat
• Colon
• Constipation
• Manometry

• Ano1
• ICC associated with submuscular plexus (ICC-SMP)
• Immunohistochemistry
• W/Wv mouse colon
• c-Kit
• colonic motility
• spatio-temporal mapping

• L-type calcium channel
• gastrointestinal motility
• irritable bowel syndrome
• otilonium bromide
• smooth muscle relaxants
• spasmolytics
• tachykinin receptor
• visceral sensitization