High amplitude propagated contractions with Glycerin versus Bisacodyl: A within-subject comparison in children undergoing colonic manometry.

BACKGROUND: The presence of high amplitude propagated contractions (HAPCs) measured by colonic manometry (CM) reflect an intact neuromuscular function of the colon. Bisacodyl and Glycerin are colonic stimulants that induce HAPCs and are used for the treatment of constipation. HAPCs characteristics with each drug have not been compared before. We aimed to compare the HAPC characteristics with Bisacodyl and Glycerin in children undergoing CM for constipation. METHODS: This is a prospective single-center cross-over study of children aged 2-18 years undergoing CM. All patients received both Glycerin and Bisacodyl during CM. They were randomized to group A with Bisacodyl first (n = 22) and group B with Glycerin first (n = 23), with 1.5 hours in between each dose. Differences in patient and HAPC characteristics between groups were summarized using descriptive statistics and compared using Chi-square test or Wilcoxon rank sum test as appropriate. KEY RESULTS: A total of 45 patients were included. HAPCs post Bisacodyl had a longer duration of action (median of 40 vs 21.5 min, p < 0.0001), longer propagation (median of 70 vs 60 cm, p = 0.02), and more HAPCs (median of 10 vs 5, p < 0.0001) compared Glycerin. No differences were found in the HAPC amplitude and onset of action between both medications.

Effect of Caffeine on Colonic Manometry in Children.

OBJECTIVES: Coffee and caffeinated products have been widely consumed for many centuries. Previous adult studies have suggested that both coffee and decaffeinated beverages induce colonic motility. However, no study has been conducted in pediatrics, and the role of caffeine alone in pediatric colonic motility needs to be explored. METHODS: A prospective study of pediatric patients undergoing standard colonic motility testing that were able to consume caffeinated coffee, decaffeinated coffee, and caffeine tablet during colonic manometry. Patients who had a gastrocolonic reflex and high amplitude propagated contractions (HAPCs) in response to intraluminal administration of bisacodyl in the colon were included in the final analyses. RESULTS: Thirty-eight patients were recruited, 22 of which were excluded, 11 due to abnormal studies (no HAPC seen in response to intraluminal response to bisacodyl), and 11 due to inability to consume all study agents or complete the study. Sixteen patients met criteria for final analyses. Intracolonic bisacodyl produced a larger area under the curve (AUC) compared to all other agents. Caffeinated coffee resulted in a higher AUC, motility index (MI), and time to HAPC compared with decaffeinated coffee ( P < 0.05). There was no significant difference between caffeinated coffee and caffeine tablet, or caffeine tablet and decaffeinated coffee. CONCLUSIONS: Caffeine is indeed a colonic stimulant; however, other components of caffeinated and non-caffeinated beverages likely induce colonic response and require further evaluation for possible use as a colonic stimulant.

Bisacodyl Limits Chikungunya Virus Replication In Vitro and Is Broadly Antiviral.

Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics. One way to facilitate development is to repurpose molecules already used clinically. By screening such compounds, we can accelerate antiviral development. Here, we screened compounds from the National Institutes of Health's Developmental Therapeutic Program for activity against chikungunya virus, an alphavirus that is responsible for a significant outbreak in the Americas in 2013. Using this library, we identified several compounds with known antiviral activity, as well as several novel antivirals. Given its favorable in vitro activity and well-described in vivo activity, as well as its broad availability, we focused on bisacodyl, a laxative used for the treatment of constipation, for follow-up studies. We find that bisacodyl inhibits chikungunya virus infection in a variety of cell types, over a range of concentrations, and over several rounds of replication. We find that bisacodyl does not disrupt chikungunya virus particles or interfere with their ability to attach to cells, but, instead, bisacodyl inhibits virus replication. Finally, we find that bisacodyl is broadly antiviral against a variety of RNA viruses, including enteroviruses, flaviviruses, bunyaviruses, and alphaviruses; however, it exhibited no activity against the DNA virus vaccinia virus. Together, these data highlight the power of compound screening to identify novel antivirals and suggest that bisacodyl may hold promise as a broad-spectrum antiviral.

Duodenal and proximal jejunal motility inhibition associated with bisacodyl-induced colonic high-amplitude propagating contractions.

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high-amplitude propagating contractions (HAPCs). Whereas the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility. Twenty-seven children (9.3 ± 1.2 yr) undergoing simultaneous high-resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed before and after colonic infusion of bisacodyl. Patients were divided into two groups: responders and nonresponders based on the presence of high-amplitude propagating contractions (HAPCs) after bisacodyl infusion. Nineteen patients were responders. A total of 188 postbisacodyl HAPCs was identified with a mean count of 10.4 ± 5.5 (range, 3-22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg. No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the nonresponders, there was no detectable change in small bowel motility after bisacodyl infusion. Bisacodyl-induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content.NEW & NOTEWORTHY The present study has shown, for the first time, that the presence of high-amplitude propagating contractions induced by bisacodyl is associated with a significant reduction in small bowel motility. These findings support of possible existence of a reflex pathway that causes inhibition of small bowel motility in response to rectal distension.

Bisacodyl Suppresses TGF-α-Induced MUC5AC Production in NCI-H292 Cells.

MUC5AC overproduction is commonly observed in chronic inflammatory lung diseases and worsens these conditions. Therefore, drugs that inhibit MUC5AC production are urgently needed. To identify novel drugs directly inhibiting MUC5AC production, 640 already approved drugs were screened. We found that the laxative bisacodyl suppressed transforming growth factor (TGF)-α-induced MUC5AC production in a concentration-dependent manner. Additionally, bisacodyl also suppressed TGF-α-induced MUC5AC mRNA expression in the same concentration range. These results suggested that bisacodyl could be a new drug for treating mucin overproduction.

Heat-inactivated Lactobacillus plantarum nF1 promotes intestinal health in Loperamide-induced constipation rats.

Constipation is a common condition that affects individuals of all ages, and prolonged constipation needs to be prevented to avoid potential complications and reduce the additional stress on individuals with pre-medical conditions. This study aimed to evaluate the effects of heat-inactivated Lactobacillus plantarum (HLp-nF1) on loperamide-induced constipation in rats. Constipation-induced male rats were treated orally with low to high doses of HLp-nF1 and an anti-constipation medication Dulcolax for five weeks. Study has 8 groups, control group; loperamide-treated group; Dulcolax-treated group; treatment with 3.2 × 1010, 8 × 1010 and 1.6 × 1011, cells/mL HLp-nF1; Loperamide + Dulcolax treated group. HLp-nF1 treated rats showed improvements in fecal pellet number, weight, water content, intestinal transit length, and contractility compared to the constipation-induced rats. Also, an increase in the intestine mucosal layer thickness and the number of mucin-producing crypt epithelial cells were observed in HLp-nF1-treated groups. Further, the levels of inflammatory cytokines levels were significantly downregulated by treatment with HLp-nF1 and Dulcolax. Notably, the metagenomics sequencing analysis demonstrated a similar genus pattern to the pre-preparation group and control with HLp-nF1 treatment. In conclusion, the administration of >3.2 × 1010 cells/mL HLp-nF1 has a positive impact on the constipated rats overall health.

High-resolution manometry reveals different effect of polyethylene glycol, bisacodyl, and prucalopride on colonic motility in healthy subjects: An acute, open label, randomized, crossover, reader-blinded study with potential clinical implications.

BACKGROUND: Polyethylene glycol (PEG), bisacodyl, and prucalopride have been reported to be more effective than placebo in treating patients with constipation but about 50% of the patients still do not respond to these medications. Only bisacodyl and prucalopride are expected to directly stimulate the colonic motility in humans in vivo. As no previous study has done this, the aim of the study was to investigate the effect of PEG, bisacodyl, and prucalopride as compared to placebo on colonic motility assessed by means of the high-resolution manometry (HRM) in healthy subjects. METHODS: Ten healthy subjects have been enrolled in an acute, open label, randomized, reader-blinded, crossover study and requested to undergo a colonoscopy-assisted HRM measuring their colonic motility before and after oral administration of 13.8 g (two doses) PEG, 10 mg bisacodyl, 2 mg prucalopride, and placebo. KEY RESULTS: In the human prepared colon, oral administration of PEG significantly increases the number of low-amplitude long distance propagating contractions (p = 0.007 vs placebo) while bisacodyl significantly increases the number of high-amplitude propagating contractions (HAPCs) (all p < 0.01 vs PEG, prucalopride, and placebo). Prucalopride has no major effect on the number of propagating contractions but increases HAPCs amplitude (p = 0.01). CONCLUSIONS & INFERENCES: In humans, PEG, prucalopride, and bisacodyl have distinct effects on colonic motility. This information has clinical implication, as it indicates that the combination of prucalopride and bisacodyl, normally not considered in clinical practice, could be effective in treating patients with constipation refractory to single medications.

Characterization of the colonic response to bisacodyl in children with treatment-refractory constipation.

BACKGROUND: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment-refractory constipation. If bisacodyl does not induce high-amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. METHODS: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. RESULTS: One hundred and sixty-five children were included (median age 10, range 1-17 years; n = 96 girls). One thousand eight hundred and ninety-three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre- vs post-bisacodyl (Z = -0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ2 (1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. CONCLUSIONS AND INFERENCES: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment-refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined.

Bowel Preparation for Colonoscopy in Children: 1 Day PEG-3350 with Bisacodyl versus 3 Day Sennosides.

BACKGROUND AND OBJECTIVES: Bowel preparation (BP) for colonoscopy is a challenging procedure in children and different regimens have been used for this purpose. Polyethylene glycol (PEG) is the most preferred agent in recent years. The primary aim of this study was to evaluate the efficacy of 1-day PEG-3350 with bisacodyl (PEG-B) and comparing it with 3-day sennosides A+B. METHOD: In this prospective, randomized, and single-blinded study, children aged 2-18 years were included in the PEG-B group for 1 day or in Senna group for 3 days. The effectiveness of BP was assessed according to the Ottawa and Boston BP scales, compliance and adverse effects were also recorded. Pre- and post-preparation biochemistry were obtained for investigation of safety of both regimens. RESULTS: Successful BP was observed in 88.3% (n = 53/60) of PEG-B and 86% (n = 55/64) of Senna groups according to Boston scale, and it was 85% (n = 51/60) and 84.4% (n = 54/64), respectively, according to Ottawa scale. The cecal intubation rate was 96.7% (n = 58/60) in the PEG-B group and 93.8% (n = 60/64) in the Senna group. Ease of administration and disturbance in regular daily activities was better in the PEG-B group (p < 0.05). There was no major adverse event and biochemical abnormality in both groups. The correlation between Ottawa and Boston scales was found to be excellent (r2 = -0.954, p < 0.01). CONCLUSIONS: The efficacy, safety, and adverse effect profile of 1-day BP with PEG-B regimen was found to be similar to 3-day sennosides regimen, however, the PEG-B regimen had advantages such as short duration, ease of administration, and better patient comfort. Also, high correlation rate between the Boston and Ottawa scales in pediatric patients was remarkable.

bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)-the active metabolite of the laxatives bisacodyl and sodium picosulfate-enhances contractility and secretion in human intestine in vitro.

BACKGROUND: Stimulant laxatives are widely used to treat constipation. We investigated in human small and large intestinal preparations the effects of bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), the active metabolite of the laxatives bisacodyl and sodium picosulfate on smooth muscle tone and epithelial secretion. METHODS: Circular and longitudinal muscle tone of small or large intestinal preparations were recorded with isometric force transducers. Epithelial ion flux (ISC ) and tissue resistance was measured with Ussing chamber technique after apical and basolateral BHPM application to large intestinal mucosa/submucosa preparations. Studies were performed in macroscopically normal specimens from 79 patients. KEY RESULTS: BHPM concentration-dependently (0.5-5 µM) increased the tone of circular and longitudinal muscle from small to large intestine. The effect was strongest in large intestinal longitudinal muscle and smallest in small intestinal circular muscle. Increase in muscle tone was prevented by the L-type Ca++ channel blocker nifedipine but insensitive to the nerve blocker tetrodotoxin. Apical or basolateral BHPM concentration-dependently decreased or increased ISC, respectively. The KCa 1.1 (BK) channel blocker iberiotoxin reversed apical ISC decrease whereas tetrodotoxin reversed basolateral ISC increase. BHPM had no effect on tissue resistance or nerve-mediated secretory or muscle response with one exception: at the highest concentration basolateral BHPM reduced nerve-mediated secretion. CONCLUSIONS AND INTERFERENCES: BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+ secretion when acting luminally and a nerve-driven Cl- and HCO3- secretion once acting basolaterally after absorption.

Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study).

BACKGROUND: Because of its volume, adequate bowel preparation remains problematic in physically unfit patients. OBJECTIVE: This study aimed to compare a small-volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid-enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol solution plus bisacodyl is 70% efficacious in achieving an Ottawa score ≤7 and accepting a difference in success rate of <15% with a target enrollment of 146 patients per group. SETTING: This study was conducted in an outpatient department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly assigned. Key exclusion criteria were severe kidney disease, ASA class ≥III, and hospital admission. INTERVENTION: Patients were randomly assigned to receive sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene glycol solution plus bisacodyl according to a split-dose regimen. Patients in the sodium picosulfate/magnesium citrate group received advice on the recommended 4-L fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel-cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used. Colonoscopy quality measures were obtained. Safety was assessed for a 30-day follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years; BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients, and 75.4% of patients used medication. An adequate Ottawa score was obtained in 81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of 5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for sodium picosulfate/magnesium citrate in the right and transverse colon. In both groups, successful ileocecal intubation was achieved in 95%. No medication-related adverse events were reported. LIMITATIONS: These results in a physically disabled ambulant population cannot be extrapolated to immobile, hospitalized patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to sodium picosulfate/magnesium citrate warrants further consideration. See Video Abstract at http://links.lww.com/DCR/A461.

Bisacodyl and its cytotoxic activity on human glioblastoma stem-like cells. Implication of inositol 1,4,5-triphosphate receptor dependent calcium signaling.

Glioblastoma is the most common malignant brain tumor. The heterogeneity at the cellular level, metabolic specificities and plasticity of the cancer cells are a challenge for glioblastoma treatment. Identification of cancer cells endowed with stem properties and able to propagate the tumor in animal xenografts has opened a new paradigm in cancer therapy. Thus, to increase efficacy and avoid tumor recurrence, therapies need to target not only the differentiated cells of the tumor mass, but also the cancer stem-like cells. These therapies need to be effective on cells present in the hypoxic, slightly acidic microenvironment found within tumors. Such a microenvironment is known to favor more aggressive undifferentiated phenotypes and a slow-growing "quiescent state" that preserves the cells from chemotherapeutic agents, which mostly target proliferating cells. Based on these considerations, we performed a differential screening of the Prestwick Chemical Library of approved drugs on both proliferating and quiescent glioblastoma stem-like cells and identified bisacodyl as a cytotoxic agent with selectivity for quiescent glioblastoma stem-like cells. In the present study we further characterize bisacodyl activity and show its efficacy in vitro on clonal macro-tumorospheres, as well as in vivo in glioblastoma mouse models. Our work further suggests that bisacodyl acts through inhibition of Ca2+ release from the InsP3 receptors.

Desacetyl bisacodyl-induced epithelial Cl(-) secretion in rat colon and rectum.

The purpose of this study was to clarify the mode of desacetyl bisacodyl (DAB)-induced secretory action in intestinal tissues using an Ussing chamber assay. DAB is the active metabolite of the laxative bisacodyl. In mucosal-submucosal preparations, mucosal application of DAB induced a transient decrease followed by subsequent increases in short-circuit current and tissue conductance in a concentration-dependent manner. DAB-induced responses occurred from the middle colon to the rectal segment but not in the proximal colon. Moreover, these responses were not observed under chloride (Cl(-))-free conditions or in the presence of DAB on the serosal side of the mucosalsubmucosal specimens. Treatment with tetrodotoxin had no effect on the DAB-induced responses; however, mucosal treatment with a COX inhibitor piroxicam resulted in the elimination of responses. These results suggest that DAB may contribute to the laxative action by inducing Cl(-) secretion which is associated with the COX signaling pathway. This study also demonstrated that the DAB target molecule is present on the mucosal side from the middle colon to the rectal segment.

Investigations of bisacodyl with modified ß-cyclodextrins: Characterization, molecular modeling, and effect of PEG.

Bisacodyl inclusion into hydroxypropyl-ß-cyclodextrin and 2,6-di-O-methyl-ß-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.

Gastrointestinal problems in 15q duplication syndrome.

Chromosome 15q duplication syndrome (Dup15q syndrome) is a neurodevelopmental disorder involving copy number gains of the maternal chromosome 15q11.2-q13 region, characterized by intellectual disability, developmental delay, autism spectrum disorder (ASD), and epilepsy. Gastrointestinal (GI) problems in Dup15q syndrome have been reported only rarely, mostly focused on neonatal feeding difficulties. A retrospective review of the medical records of 46 patients with Dup15q syndrome was conducted to assess GI issues and their treatments in this population. GI symptoms were present in 76.7% of subjects with an isodicentric duplication and 87.5% with an interstitial duplication. There was no clear association between GI issues and ASD, with symptoms occurring in 78.9% of all subjects and 78.2% of ASD subjects. The most commonly reported symptoms were gastroesophageal reflux (56.7%) and constipation (60%), with 30% of subjects reporting both. The most common treatments were polyethylene glycol for constipation and proton pump inhibitors for reflux. Behaviors such as irritability and aggressiveness improved with treatment of GI symptoms in several subjects. The results indicate that GI symptoms are common in Dup15q syndrome and may have an atypical presentation. Diagnosis may be difficult, especially in individuals who are nonverbal or minimally verbal, so increased awareness is critical for early diagnosis and treatment.

Bowel cleansing before CT colonography: comparison between two minimal-preparation regimens.

AIM: To compare two regimens of reduced bowel preparation and faecal tagging for CT colonography. MATERIALS AND METHODS: Single centre, prospective, randomized, noninferiority study, in which 52 consecutive adults underwent routine CT colonography. Patients, following a three-day low-fibre diet, received one of the two reduced preparations: 1-L polyethylene glycol and four tablets of bisacodyl in association with 90 mL of Iopamidol for faecal tagging administered on the same day as CTC examination (group 1); or a standard "iodine-only" preparation, consisting in 180 ml of Iopamidol the day before the examination (group 2). Primary outcome was the overall quality of bowel preparation. RESULTS: Twenty-six patients per group were included. Per segment analysis showed preparation of diagnostic quality in 97.4% of segments in group 1 and in 95.5% in group 2 (p = ns). Per-patient analysis showed optimal quality of preparation in 76.9% of patients in group 1 and in 84.6% in group 2 (p = ns). Patient tolerability to both preparations was not different. CONCLUSION: A limited bowel preparation consisting of 1-L PEG and four tablets of bisacodyl in association with 90 mL of Iodine for faecal tagging administered on the same day as CTC examination is feasible and offers bowel cleansing comparable to "iodine-only" preparation. KEY POINTS: • Low-dose PEG bisacodyl and Iopamidol preparation is feasible, providing adequate bowel cleansing. • Faecal tagging is not different from the two limited preparations. • Patient tolerability to the two colon cleansing regimens is similar.

Colon high-resolution manometry: using pressure topography plots to evaluate pediatric colon motility.

OBJECTIVES: Colon manometry is usually performed using the 8-pressure sensor water-perfused manometry system. High-resolution manometry (HRM), using closely spaced solid-state pressure recording sensors, provides more detailed information of gut luminal pressure changes, and, by displaying the HRM data as a pressure topography plot (PTP), helps with data interpretation. Our aim was to compare the colon and rectal luminal pressure data obtained using 8 pressure sensors and displayed as conventional line plot (CLP) with data obtained using a custom-made solid state manometry catheter with 36 pressure recording sensors and displayed as PTP. METHODS: We evaluated colon manometry patterns during fasting, response to meal, and bisacodyl stimulation in 10 patients with constipation and stool expulsion disorders. The data from 8 pressure sensors were displayed as CLP and data from 36 pressure sensors as PTP. Two gastroenterologists independently interpreted these studies. We calculated variability in interpreting colon, rectal, and anal manometry data. RESULTS: Intermode, interobserver, and intraobserver reliability were good to excellent for recognizing colon contraction patterns when data are displayed as PTP compared with when displayed as CLP, whereas the reliability for recognizing anal contractions were poor to excellent. CONCLUSIONS: Colonic and anal manometry patterns are easily recognized when HRM data are expressed as PTP. Obtaining information of colonic luminal pressure changes with rectum and anal pressure changes using HRM can help better understand the pathophysiology of pediatric constipation and stool expulsion disorders.

[The elucidation of the function and the expression control mechanism of aquaporin-3 in the colon].

Aquaporins (AQPs) are membrane channels that transport water within the human body and are therefore important for the regulation of water homeostasis. However, little is known regarding the details of the physiological role of AQP3, which is predominantly expressed in the colon. Thus, we investigated the role of AQP3 in the colon using laxative agents (magnesium sulfate and bisacodyl). The results suggest that the laxative effect produced by magnesium sulfate, which is classified as an osmotic laxative, is not simply a result of the changes in osmotic pressure but is also associated with the increased expression of AQP3 in the mucosal epithelial cells of the colon. In addition, magnesium sulfate increased colonic AQP3 expression through adenylate cyclase activation, which is caused by an increase in the intracellular Mg(2+) concentration. This effect may trigger CREB phosphorylation through PKA activation and promote AQP3 gene transcription. Meanwhile, bisacodyl, which is classified as a stimulant laxative, decreases the expression level of AQP3 in the mucosal epithelial cells of the colon, resulting in the inhibition of water transfer from the intestinal tract to the vascular side of the epithelium, eventually leading to the development of diarrhea. It was also observed that the direct activation of colon macrophages by bisacodyl increases the secretion of PGE2, which acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Future studies of the enteric AQP3 expression level and water transport may aid in the development of new laxative and antidiarrheal agents that target AQP3.

Impact of colonoscopy bowel preparation on intestinal microbiota.

The gut microbiota is important in maintaining human health, but numerous factors have the potential to alter its composition. Our aim was to examine the impact of a standard bowel preparation on the intestinal microbiota using two different techniques. Fifteen subjects undergoing colonoscopy consumed a bowel preparation comprised of 10 mg bisacodyl and 2 L polyethylene glycol. The microbiota of stool samples, collected one month before, one week before (pre-colonoscopy), and one week, one month, and three to six months after colonoscopy (post-colonoscopy) was evaluated. Two samples were taken three to six months apart from five healthy subjects who did not undergo colonoscopy. Universal primers targeting the V2-V3 region of the 16S rRNA gene were used to PCR amplify all samples for denaturing gradient gel electrophoresis (PCR-DGGE). Pre- and post-colonoscopy samples were compared using Dice's similarity coefficients. Three samples from ten subjects who underwent colonoscopy, and both samples from the five subjects who didn't, were used for high-throughput sequencing of the V1-V3 region of the 16S rRNA gene. Samples were curated and analysed in Mothur. Results of the DGGE analyses show that the fecal microbiota of a small number of subjects had short-term changes. High-throughput sequencing results indicated that the variation between the samples of subjects who underwent colonoscopy was no greater than the variation observed between samples from subjects who did not. We conclude that bowel preparation does not have a lasting effect on the composition of the intestinal microbiota for the majority of subjects.

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

BACKGROUND: New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. OBJECTIVE: This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). DESIGN: Multicenter, assessor-blinded, randomized, noninferiority study. SETTING: University hospitals, academic medical centers, and private clinics across the United States. PATIENTS: Adults preparing for colonoscopy. INTERVENTIONS: P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. MAIN OUTCOME MEASUREMENTS: This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. RESULTS: The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). LIMITATIONS: Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. CONCLUSIONS: The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets.