Small Intestinal Transit Time Research Articles

PULSATILE DRUG DELIVERY SYSTEMS THE NOVEL APPROACH

Oral pulsatile drug delivery systems (PDDS) are intended to induce programmable lag phases before a quick and quantifiable, repeated, or prolonged medication release. As a result, they are gaining popularity due to their inherent suitability for achieving chronotherapeutic goals, which have just been highlighted concerning several prevalent chronic illnesses characterized by typical night or early-morning recurring symptoms (e. g. bronchial asthma, heart attack, rheumatoid arthritis, early-morningawakening). Furthermore, time-based colonic release is possible when pulsatile delivery devices are correctly modified to overcome unexpected gastric emptying and give delay periods that roughly match the small intestine transit time. Oral pulsatile administration is accomplished using several release platforms, including reservoir, capsular, and osmotic devices. The current review article addressed the topics that followed: the reason pulsatile drug delivery systems have been invented; diseases for which pulsatile release is necessary; classification, advantages and disadvantages; methods used in the current systems; the situation nowadays and its potential for the future; recent advancements, and especially, the previous five to ten years of research on pulsatile drug delivery conducted by researchers using a variety of drugs for a variety of diseases.

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

Effects of Bit Chewing on Gastric Emptying, Small Intestinal Transit, and Orocecal Transit Times in Clinically Normal Horses.

Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.

Alternate-day fasting induces metabolic and morphofunctional changes in the gastrointestinal tract of male rats.

Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n=8), control for 30 days (CON 30, n=8), ADF for 15 days (ADF 15, n=8), and ADF for 30 days (ADF 30, n=8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.

Physiologically based pharmacokinetic modeling to predict OAT3-mediated drug-drug interactions of meropenem in varying stages of chronic kidney disease

ObjectiveThis study aimed to predict OAT3-mediated meropenem DDIs in varying stages of CKD using physiologically based pharmacokinetic (PBPK) models. MethodsMeropenem DDI model was performed with OAT3 perpetrators probenecid (strong inhibitor), piperacillin (moderate inhibitor) and acyclovir (weak inhibitor). Firstly, whole-body PBPK models were developed for meropenem and piperacillin in healthy adults with PK-Sim®. Then the models were translated to patients with varying stages of CKD by accounting for changes in eGFR, kidney volume, kidney blood flow, hematocrit, gastric emptying time, small intestinal transit time, OAT transport function and non-renal clearance. Subsequently, meropenem DDI model was verified by comparing the model simulation results of the interaction between meropenem and probenecid with the observational data from clinical studies. Finally, pharmacokinetics of meropenem under co-administration of piperacillin and acyclovir were predicted through simulations with the virtual population in varying stages of CKD. ResultsThe developed PBPK models of meropenem and piperacillin adequately described the pharmacokinetic characteristics in healthy adults and in adults with varying stages of CKD. The predicted AUC ratio of meropenem co-administered with probenecid to meropenem given alone was within 1.5-fold of the observed clinical data. The predicted steady-state AUC values of meropenem in healthy adults co-administered with probenecid, piperacillin or acyclovir were 1.593-fold (95% CI, 1.436-1.6244), 1.031-fold (95% CI, 1.017-1.045) and 1.005-fold (95% CI, 1.004-1.005), respectively, as compared to the AUC of meropenem given alone. And all predicted probenecid-meropenem, piperacillin-meropenem and acyclovir-meropenem DDI AUC ratios were decreased in renal impairment. Our presented meropenem DDI model demonstrated that patients with CKD may be less vulnerable to OAT3-mediated DDIs compared with healthy adults. However, further clinical DDI studies are required to verify our prediction results. ConclusionPBPK analysis provided a quantitative basis for guiding the clinical application of meropenem combined with OAT3 inhibitor in varying stages of CKD.

Wireless Monitoring of Gastrointestinal Transit Time, Intra-luminal pH, Pressure and Temperature in Experimental Pigs: A Pilot Study

Background: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. Aims: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. Methods: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. Results: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5–34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. Conclusions: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

Time-Based Formulation Strategies for Colon Drug Delivery.

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed.

Effect of ceftriaxone on intestinal transit time.

Ceftriaxone reduces gallbladder and ileal contractility. Many studies have shown that ceftriaxone causes biliary sludge and pseudolithiasis. However, its effect on intestinal transit time has not been investigated. This study aimed to investigate the effect of ceftriaxone on intestinal transit time. Sixteen rats were examined in two groups: The study group (group A, n= 8) was administered with 100 mg/kg ceftriaxone intramuscularly for 7days. The control group (group B, n= 8) was administered with intramuscular distilled water for 7days. On the seventh day, a mixture of 2ml barium and saline was given orally to both groups. Barium transit was evaluated using serial digital X-ray images. The stomach was full and the transition into the small intestine loop was observed in all rats at 45 min in both groups. At the 2nd hour, colonic transition was observed in two rats in group A (2/8, 25%) and in seven rats in group B (7/8, 87.5%). At the 4th hour, five (62.5%) rats in group A had transverse colonic transition, and all rats in group B (8/8, 100%) had transverse and/or left colonic transition. At the 6th hour, no rat in group A had rectal transition, and all rats in group B (8/8, 100%) had complete passage of colonic contrast material. Ceftriaxone significantly prolongs the small intestine transit time, large intestine transit time, and total intestinal transit times.

Regional gastrointestinal transit times in patients with chronic pancreatitis.

The mechanisms behind disrupted gastrointestinal (GI) motor function in patients with chronic pancreatitis (CP) have not been fully elucidated. We compared regional transit times in patients with CP to those in healthy controls, and investigated whether they were associated with diabetes mellitus, exocrine dysfunction, opioid treatment or quality of life. Twenty-eight patients with CP and 28 age- and gender-matched healthy controls were included. Regional GI transit times were determined using the 3D-Transit system, which consists of an ingestible electromagnetic capsule and a detector worn in an abdominal belt for 5 days. Exocrine function was assessed using the fecal elastase-1 test, and quality of life was assessed using the European Organization for Research and Treatment of Cancer questionnaire. Transit times were analyzed for associations with diabetes mellitus, exocrine pancreatic insufficiency (EPI), opioid treatment and quality of life. Compared with healthy controls, patients with CP had prolonged transit times in the small intestine (6.6 ± 1.8 vs 4.8 ± 2.2 hours, P = .006), colon (40 ± 23 vs 28 ± 26 hours, P = .02), and total GI tract (52 ± 26 vs 36 ± 26 hours, P = .02). There was no difference in gastric emptying time (4.8 ± 5.2 vs 3.1 ± 1.3 hours, P = .9). No associations between transit times and diabetes, EPI, or opioid consumption were found (all P > .05). Quality of life and associated functional and symptom subscales were not associated with transit times, except for diarrhea (P = .03). Patients with CP have prolonged small intestinal and colonic transit times. However, these alterations do not seem to be mediated by diabetes, EPI, or opioid consumption.

S1566 Evaluation of the Pharmacokinetics of PGN-OB1 Following Oral Administration of an Oral Biotherapeutics Delivery System (OBDS) in Yucatan Swine

Introduction: Biologics/peptides/nucleic acids are highly effective drugs; however, oral delivery of these therapeutics has proved to be difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and the poor absorption rate in the small intestinal mucosa. We aimed to develop an oral biotherapeutic delivery system (OBDS) that protects these biomolecules from degradation in the upper GIT and increases oral bioavailability via needless injection in the submucosal space of the small intestine. We describe the development of models to assess the functional capability of the OBDS capsule. A Yucatan minipig model was chosen to better represent the pharmacokinetic properties of submucosal injection in humans and evaluate the injection efficiency of OBDS in vivo. Methods: Due to prolonged and variable gastric residence times in the swine model, the semi-autonomous OBDS capsules containing a variant of adalimumab (PGN-001), PGN-OB1, were administrated by intraduodenal endoscopic placement (ID) and released into the proximal small intestines of the female Yucatan swine. Blood samples post-ID dosing were collected to evaluate the injection efficiency of the OBDS compared with the IV control group. Results: All OBDS capsules were successfully advanced through the pyloric sphincter via endoscopic placement, without early deployment, and released in the proximal duodenum to naturally transit and deploy in vivo. Out of 13 animals dosed, 8 animals showed detectable drug levels (Figure), and an oral bioavailability average of 22% or 25% (range from 7-55%) excluding an animal showing a late deployment at 72hr post-dose. The variability in the swine model is believed to be due to physiologic variability that may not directly translate to humans including variability in small intestinal transit time, and more frequent and larger, gas and fluid pockets in the swine. Conclusion: Here we have provided proof-of-concept of a semi-autonomous OBDS device that can achieve as high as 55% bioavailability of a variant of adalimumab that is a magnitude higher than current oral protein or peptide delivery technology in the market and at levels much closer to the subcutaneous route of administration estimated in human trials. The OBDS capsules could potentially provide a better alternative for the non-invasive route of administration with better patient compliance.Figure 1.: Plasma concentration of PGN-001 treated with ID and IV over time

Physiologically based Pharmacokinetic Models under the Prism of the Finite Absorption Time Concept.

To date, mechanistic modeling of oral drug absorption has been achieved via the use of physiologically based pharmacokinetic (PBPK) modeling, and more specifically, physiologically based biopharmaceutics model (PBBM). The concept of finite absorption time (FAT) has been developed recently and the application of the relevant physiologically based finite time pharmacokinetic (PBFTPK) models to experimental data provides explicit evidence that drug absorption terminates at a specific time point. In this manuscript, we explored how PBBM and PBFTPK models compare when applied to the same dataset. A set of six compounds with clinical data from immediate-release formulation were selected. Both models resulted in absorption time estimates within the small intestinal transit time, with PBFTPK models generally providing shorter time estimates. A clear relationship between the absorption rate and the product of permeability and luminal concentration was observed, in concurrence with the fundamental assumptions of PBFTPK models. We propose that future research on the synergy between the two modeling approaches can lead to both improvements in the initial parameterization of PBPK/PBBM models but to also expand mechanistic oral absorption concepts to more traditional pharmacometrics applications.

Magnetically controlled capsule endoscopy in one-time gastro-small intestinal joint examination: a two-centre experience

BackgroundThe lesions of certain diseases are widely distributed in both stomach and small intestine, while the step-by-step strategy of gastroscopy followed by enteroscopy can be burdensome and costly. We aimed to determine if magnetically controlled capsule endoscopy (MCE) could be used in one-time gastro-small intestine (GSI) joint examination.MethodsIn this study, data of patients in Chinese PLA General Hospital and Changhai Hospital who underwent MCE GSI examination from January 2020 to August 2021 were retrospectively analysed. The primary outcome of this study was the success rate of one-time GSI joint examination, and secondary outcomes included visualization and cleanliness of gastrointestinal tract, gastrointestinal transit times, diagnostic yield and safety of MCE examination.ResultsA total of 768 patients were included. The success rate of one-time GSI joint examination was 92.58%. There were 94.92% MCEs observed > 90% gastric mucosa in the 6 anatomic landmarks. The rate of complete small bowel examination was 97.40%. The median gastric examination time, gastric transit time and small intestine transit time were 8.18 min, 63.89 min and 4.89 h, respectively. Magnetic steering of MCE significantly decreased gastric transit time (8.92 min vs. 79.68 min, P = 0.001) and increased duodenal lesion detection rate (13.47% vs. 6.26%, P = 0.001) when compared with non-magnetic steering group. Two capsules were retained and were removed by enteroscopy or spontaneously excreted.ConclusionsMCE is feasible to complete GSI joint examination and the detection of both gastric and small intestinal diseases can be achieved simultaneously.Trial registration Clinical Trial Registration ClinicalTrials.gov, ID: NCT05069233.

The Impact of Metabolic Risk Factors, Diabetes, Medications, and Comorbid Illness on Transit Time at Capsule Endoscopy: A Prospective Cohort Study

Background: Video capsule endoscopy (VCE) is a safe and effective way of investigating obscure gastrointestinal bleeding. One of the main limitations of VCE is suboptimal visualisation due to prolonged gastric transit time (GTT) or rapid small intestinal transit time (SITT). The role of metabolic risk factors, diabetes, and medications on transit times remains unclear. Aim: The aim of this study was to assess the impact of diabetes, obesity, medications, and metabolic syndrome on transit times at VCE. Method: The study performed was a single centre, observational study. Results: Significant predictors of decreased GTT were increasing age and use of beta blocker medication. No predictive factors for increased GTT were identified. Significant predictors of decreased SITT on univariate analysis were increased GTT, serum glucose >5mmol/L, obesity, and diabetes. On multivariate analysis, increased GTT and glucose remained significant. Conclusions: Beta-blocker therapy reduces GTT. Hyperglycaemia at the time of VCE reduces SITT. These allow for possible therapeutic strategies to improve the diagnostic yield at VCE.

Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy.

Background/AimsPatients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms.MethodsTwenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans.ResultsPatients with DM and HCs did not differ with regard to median gastric contraction frequency (DM 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM 9 mm [IQR, 8-11]; HCs 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM 149 cm3 [IQR, 112-187]; HCs 132 cm3 [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM 3.3 hours [IQR, 2.6-4.6]; HCs 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM 5 hours [IQR, 3.7-5.6]; HCs 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM 623 cm3 [IQR, 487-766]; HCs 478 cm3 [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs.ConclusionIn our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy.

Regional Gastrointestinal Motility in Healthy Children.

The aim of the study was to evaluate the safety and use of the 3D-Transit system (Motilis SA, Lausanne, Switzerland) and to describe regional gastrointestinal transit times, segmental colonic transit times, and colonic movement patterns in healthy children. Twenty-one healthy children (11 girls, median age 10.5 years, range 7-15 years) were included. For evaluation of gastrointestinal transit times and colonic movement patterns, we used the minimally invasive electromagnetic 3D-Transit system. A small electromagnetic capsule (21.5 mm × 8.3 mm) was ingested and tracked through the gastrointestinal tract by a body-worn detector. Regional gastrointestinal transit times were assessed as time between capsule passage of anatomical landmarks. Colonic movement patterns were described and classified based on capsule movement velocity, direction, and distance. One child could not swallow the capsule and 20 children completed the study without any discomfort or side-effects. Median whole gut transit time was 33.6 (range 10.7-80.5) hours, median gastric emptying time was 1.9 (range 0.1-22.1) hours, median small intestinal transit time was 4.9 (range 1.1-15.1) hours, and median colonic transit time was 26.4 (range 6.8-74.5) hours. Median ascending colon/cecum transit time was 9.7 (range 0.3-48.1) hours, median transverse colon transit time was 5.6 (range 0.0-11.6) hours, median descending colon transit time was 2.6 (range 0.01-22.3) hours, and median sigmoid colon/rectum transit time was 7.5 (range 0.1-31.6) hours. Colonic movement patterns among children corresponded to those previously described in healthy adults. The 3D-Transit system is a well-tolerated and minimally invasive method for assessment of gastrointestinal motility in children.

The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM).

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics. The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one.

The Impact of Dextran Sodium Sulfate-Induced Gastrointestinal Injury on the Pharmacokinetic Parameters of Donepezil and Its Active Metabolite 6-O-desmethyldonepezil, and Gastric Myoelectric Activity in Experimental Pigs.

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20–30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.

Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring.

The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

Evaluation of a dual-purpose contrast medium for radiography and ultrasonography of the small intestine in dogs.

To evaluate a contrast medium that could be used for radiographic and ultrasonographic assessment of the small intestine in dogs. 8 healthy adult Beagles. Carboxymethylcellulose (CMC; 0.5% solution) was combined with iohexol (300 mg of iodine/mL) to yield modified contrast medium (MCM). Dogs were orally administered the first of 3 MCMs (10 mL/kg [9.5 mL of CMC/kg plus 0.5 mL of iohexol/kg]). Radiographic and ultrasonographic assessment of the small intestine followed 10 minutes after administration and every 10 minutes thereafter, until MCM was seen within the ascending colon. Minimally, 1 week elapsed between dosing of subsequent MCMs (10 mL/kg [9 mL of CMC/kg plus 1 mL of iohexol/kg and 8.5 mL of CMC/kg plus 1.5 mL of iohexol/kg]) and repeated radiography and ultrasonography. Radiographic contrast enhancement of the small intestine was best with MCM that combined 8.5 mL of CMC/kg and 1.5 mL of iohexol/kg. Mean small intestinal transit time for all MCMs was 86 minutes. All MCMs did not interfere with ultrasonographic assessment of the small intestine and may have improved visualization of the far-field small intestinal walls. An MCM that combined 8.5 mL of 0.5% CMC/kg and 1.5 mL of iohexol/kg could be an alternative to barium or iohexol alone for contrast small intestinal radiography in dogs, especially when abdominal ultrasonography is to follow contrast radiography.

Assessment of postoperative gastrointestinal motility in colorectal surgery: a study with the Motilis 3D-transit system

PurposePostoperative recovery following colorectal surgery remains impaired by severe complications including postoperative ileus (POI). Human studies of POI have been limited by a lack of safe and easy-to-use objective methods....