D-xylose Absorption Research Articles

Protective Effect of Coated Benzoic Acid on Intestinal Epithelium in Weaned Pigs upon Enterotoxigenic Escherichia coli Challenge.

The study was designed to investigate the protective effect of dietary supplementation with coated benzoic acid (CBA) on intestinal barrier function in weaned pigs challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two pigs were randomized to four treatments and given either a basal diet or a basal diet supplemented with 3.0 g/kg CBA, followed by oral administration of ETEC or culture medium. The results showed that CBA supplementation increased the average daily weight gain (ADWG) in the ETEC-challenged pigs (p < 0.05). CBA also increased the serum activity of total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), as it decreased the serum concentrations of endotoxin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the ETEC-challenged pigs (p < 0.05). Interestingly, the CBA alleviated the ETEC-induced intestinal epithelial injury, as indicated by a reversal of the decrease in D-xylose absorption and a decrease in the serum levels of D-lactate and diamine oxidase (DAO) activity, as well as a decrease in the quantity of apoptotic cells in the jejunal epithelium following ETEC challenge (p < 0.05). Moreover, CBA supplementation significantly elevated the mucosal antioxidant capacity and increased the abundance of tight junction protein ZO-1 and the quantity of sIgA-positive cells in the jejunal epithelium (p < 0.05). Notably, CBA increased the expression levels of porcine beta defensin 2 (PBD2), PBD3, and nuclear factor erythroid-2 related factor 2 (Nrf-2), while downregulating the expression of toll-like receptor 4 (TLR4) in the jejunal mucosa (p < 0.05). Moreover, CBA decreased the expression levels of interleukin-1β (IL-1β), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) in the ileal mucosa upon ETEC challenge (p < 0.05). These results suggest that CBA may attenuate ETEC-induced damage to the intestinal epithelium, resulting in reduced inflammation, enhanced intestinal immunity and antioxidant capacity, and improved intestinal epithelial function.

SAT028 Beneficial Effect On Intestinal Growth Of A Long-Acting GLP-2 Analog, HM15912, After Treatment Switching From Conventional GLP-2 Drug Or Other Long-Acting GLP-2 Analogs Under Clinical Development In Animal Model

Abstract Disclosure: C. Park: Employee; Self; Hanmi Pharm. Co., Ltd. J. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. E. Park: Employee; Self; Hanmi Pharm. Co., Ltd. H. Kwon: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: Employee; Self; Hanmi Pharm. Co., Ltd. D. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. The widespread use of teduglutide, which is only approved GLP-2 analog drug for short bowel syndrome (SBS), may be still limited due to insufficient efficacy and leading to a significant burden for patients by daily administration. Hence, several long-acting GLP-2 analog drugs targeting once a week are currently in clinical development. Here, we investigated that HM15912, a novel long-acting GLP-2 analog, enabled to achieve additional small bowel trophic effect after switching from those existing GLP-2 analogs. To investigate additional intestinotrophic efficacy after switching from teduglutide to HM15912, C57BL/6 mice treated with twice daily administration of teduglutide for 2 weeks were switched to once-weekly administration of HM15912, or continued the typical treatment of teduglutide for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI (72.9% over vehicle) compared to teduglutide treated group (39.4% over vehicle) after 2 weeks. After 2 more weeks treatment, while showing the maintained the increased SI weight in teduglutide treated group (58.3% at week 3 and 41.1% at week 4 over vehicle), SI weight was further increased after switching to HM15912 (61.2% at week 3 and 68.5% at week 4 over vehicle). Next, we synthesized GLP-2 analogs to have same sequences with glepaglutide and apraglutide. SD rats treated with every other day administration of these long acting GLP-2 analogs for 2 weeks were switched to HM15912 or continued the typical treatment of them for the remaining 2 weeks. HM15912 treatment significantly increased wet weight of SI compared to weekly GLP-2 analog drug treated groups after 2 weeks (84.4% versus 41.5% or 26.6% over vehicle). After 2 more weeks treatment, while showing the slight increment in SI weight in the long-acting GLP-2 analogs (50.5% and 37.4% over vehicle), SI weight was further increased after switching to HM15912 (82.1% and 90.7% over vehicle, respectively). In line with these results, D-xylose absorption capacity was also significantly increased after switching from existing GLP-2 analogs to HM15912. As a results, HM15912 significantly promoted small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of once a week in rodents. A phase 2 clinical study of once-monthly dosing in patients with SBS is ongoing to evaluate the clinical relevance of these findings. Presentation: Saturday, June 17, 2023

Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption.

Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

Pterostilbene Attenuates High-Intensity Swimming Exercise-Induced Glucose Absorption Dysfunction Associated with the Inhibition of NLRP3 Inflammasome-Induced IECs Pyroptosis

The study investigated the effect of pterostilbene (PTE) on intestinal glucose absorption and its underlying mechanisms in high-intensity swimming exercise (HISE)-treated mice. Male C57BL/6 mice were treated with PTE for 4 weeks and performed high-intensity swimming training in the last week. Intestinal epithelial cells (IECs) were pretreated with 0.5 and 1.0 μM PTE for 24 h before being incubated in hypoxia/reoxygenation condition. Intestinal glucose absorption was detected by using an oral glucose tolerance test and d-xylose absorption assay, and the levels of factors related to mitochondrial function and pyroptosis were measured via western blot analyses, cell mito stress test, and quantitative real-time polymerase chain reaction. In vivo and in vitro, the results showed that PTE attenuated HISE-induced intestinal glucose absorption dysfunction and pyroptosis in mice intestine. Moreover, PTE inhibited NLRP3 inflammasome and the mitochondrial homeostasis as well as the ROS accumulation in IEC in vitro. Additionally, knockdown of SIRT3, a major regulator of mitochondria function, by siRNA or inhibiting its activity by 3-TYP abolished the effects of PTE on pyroptosis, mitochondrial homeostasis, and ROS generation of IEC in vitro. Our results revealed that PTE could alleviate HISE-induced intestinal glucose absorption dysfunction associated with the inhibition of NLRP3 inflammasome-induced IECs pyroptosis.

ANTIOXIDANT TREATMENTS IN THE PROPHYLAXIS OF INTESTINAL REPERFUSION DAMAGE

Abstract Introduction Intestinal ischemia-reperfusion is still a relevant clinical problem, especially in newborns and in the elderly. In this piece of work, we check the utility of curcumin and dexmedetomidine to overcome the damage induced by reperfusion, both locally and in distant organs, using α-tocopherol as a comparison. Methods In female Wag/RijHsd rats, the superior mesenteric artery was clamped for 1 h; then, animals were allowed 4 h of reperfusion. Curcumin (200 mg/kg, oral) was given 24 h and 2 h before clamping; α-tocopherol (20 mg/kg, i.p.) was administered 2 h before ischemia, and dexmedetomidine (10 or 40 mg/kg, s.c.; dex-10 and dex-40, respectively) was given 15 minutes before ischemia. Blood samples and terminal ileum were collected. Additionally, a D-xylose absorption test was performed to evaluate intestinal absorption; 1h after D-xylose administration, D-xylose plasma levels were quantified (mg/ml). Results All of the treatments reduced histological damage assessed with Chiu's scale (non-treated, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; dex-10, 1.47 ± 0.7; dex-40 1.43 ± 0.9; α-tocopherol, 1.01 ± 0.8) and improved absorption of D-xylose (healthy rats 2.06 ± 0.07; non-treated, 1.18 ± 0.07; curcumin 1.76 ± 0.30; dex-10, 2.29 ± 0.20; dex-40, 2.25 ± 0.26; α-tocopherol 1.66 ± 0.21). Dexmedetomidine improved renal function (it reduced both creatinine and urea in serum). The elevation of liver enzymes in serum was not improved by any of the drugs. Conclusions The three drugs proved to be useful, though α-tocopherol was more efficient regarding histological damage, and only dexmedetomidine restored D-xylose absorption to normal values.

A starch-rich treat affects enteroinsular responses in ponies.

To determine the effect of a starch-rich treat, added to the daily diet of ponies for 10 days, on enteroinsular responses to meal consumption. 10 mixed-breed adult ponies owned by Queensland University of Technology were used in the study. Six ponies were metabolically healthy, and 4 were insulin dysregulated at the start of the study, according to the results of an in-feed oral glucose test. A bread-based treat was offered twice daily for 10 days, adding 0.36 ± 0.04 g/kg body weight (BW) carbohydrates to the daily diet. Before and after treatment, the intestinal capacity for simple carbohydrate absorption was approximated with a modified D-xylose absorption test. Plasma glucagon-like peptide-2 (GLP-2), blood glucose, and serum insulin responses to eating were also measured before and after treatment. The absorption of D-xylose (area under the curve [AUC]) increased 1.6-fold (P < .001) after 10 days of eating the treat. In addition, while basal (fasted) GLP-2 concentrations were not affected, GLP-2 AUC increased 1.4-fold in response to eating (P = .005). The treat did not change blood glucose or serum insulin concentrations, before, during, or after eating. A small amount of additional carbohydrate each day in the form of a treat can cause a measurable change in the enteroinsular responses to eating.

HM15912, a Novel Long-Acting Glucagon-Like Peptide-2 Analog, Improves Intestinal Growth and Absorption Capacity in a Male Rat Model of Short Bowel Syndrome.

Extensive bowel resection caused by various diseases that affect the intestines, such as Crohn's disease, volvulus, and cancer, leads to short bowel syndrome (SBS). Teduglutide is the only approved glucagon-like peptide-2 (GLP-2) drug for SBS; however, it requires daily administration. A novel GLP-2 analog with a prolonged duration of action to reduce dosing frequency and promote a greater efficacy may provide patients with a better quality of life. In the present study, the sustained exposure of HM15912 was characterized in normal male rats. The efficacy of HM15912 on intestinal growth and absorption capacity was also evaluated in normal male mice, rats, and SBS rats. HM15912 exhibited a remarkably extended half-life (42.3 hours) compared with teduglutide (0.6 hours) in rats. Despite somewhat lower in vitro potency on GLP-2 receptor than human GLP-2 or teduglutide, this longer-lasting mode of action promotes HM15912 to be more effective in terms of small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of as little as once a week in rodents, including SBS rats. Furthermore, the small intestinal weight was approximately doubled, and the D-xylose absorption was significantly increased after pre-treatment of existing GLP-2 analogs on the market or under clinical development followed by HM15912 in rodents. These results indicate that HM15912 possesses a significant small bowel trophic effect driven by continuously increased exposure, supporting that HM15912 may be a novel treatment option with greater efficacy and the longest dosing interval among existing GLP-2 analogs for SBS with intestinal failure. SIGNIFICANCE STATEMENT: HM15912, a novel long-acting glucagon-like peptide-2 (GLP-2) analog, has a significant small bowel hypertrophic effect in rodents with a reduced frequency of administration compared to the existing GLP-2 analogs on the market or currently under clinical development. This study supports the possibility that HM15912 could be administered much less frequently than other long-acting GLP-2 analogs for patients with short bowel syndrome.

Agrobacterium sp. ZX09 β-Glucan Attenuates Enterotoxigenic Escherichia coli-Induced Disruption of Intestinal Epithelium in Weaned Pigs.

To explore the protective effect of dietary β-glucan (BGL) supplementation on intestinal epithelium exposure to enterotoxigenic Escherichia coli (ETEC), thirty-two weaned pigs were assigned to four groups. Pigs were fed with a basal diet or basal diet containing 500 mg/kg BGL, and were orally infused with ETEC or culture medium. Results showed BGL supplementation had no influence on growth performance in weaned pigs. However, BGL supplementation increased the absorption of D-xylose, and significantly decreased the serum concentrations of D-lactate and diamine oxidase (DAO) in the ETEC-challenged pigs (p < 0.05). Interestingly, BGL significantly increased the abundance of the zonula occludens-1-(ZO-1) in the jejunal epithelium upon ETEC challenge (p < 0.05). BGL supplementation also increased the number of S-phase cells and the number of sIgA-positive cells, but significantly decreased the number of total apoptotic cells in the jejunal epithelium upon ETEC challenge (p < 0.05). Moreover, BGL significantly increased the duodenal catalase (CAT) activity and the ileal total superoxide dismutase (T-SOD) activity in the ETEC-challenged pigs (p < 0.05). Importantly, BGL significantly decreased the expression levels of critical inflammation related proteins such as the tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in the jejunal and ileal mucosa upon ETEC challenge (p < 0.05). BGL also elevated the propanoic acid content and the abundance of Lactobacillus and Bacillus in the colon upon ETEC challenge (p < 0.05). These results suggested BGL could alleviate the ETEC-induced intestinal epithelium injury, which may be associated with suppressed inflammation and improved intestinal immunity and antioxidant capacity, as well as the improved intestinal macrobiotic.

Gastrointestinal biopsy in the horse: overview of collection, interpretation, and applications.

Evaluation of gastrointestinal (GI) biopsies is a multistep process that includes reviewing an appropriate history, determining sample quality, and evaluating histologic sections. Selected diagnostic parameters that, in combination with intestinal histopathology, can be useful to localize disease to the intestinal tract in the horse include hypoproteinemia and hypoalbuminemia, ultrasound evidence of increased thickness of the small intestinal wall, and alterations in glucose or D-xylose absorption tests. Biopsies may be acquired either endoscopically, or via laparoscopy or standing flank incisional approaches. GI sections should be evaluated using a systematic approach that includes both architectural changes and inflammatory cell infiltrates. Although strategies have been developed for assessment of GI biopsies from the dog and cat, a standardized approach to interpretation of the equine GI biopsy has yet to be developed. GI biopsies pose several challenges to the pathologist, especially for endoscopic biopsies in which the quality of the specimen and its orientation may vary greatly. Architectural changes are arguably the most critical changes to evaluate. In a horse with chronic GI inflammation, such as occurs in idiopathic inflammatory bowel disease (IBD), the cell types encountered frequently are macrophages, eosinophils, lymphocytes, and plasma cells. Increased numbers of these cell types are categorized loosely as mild, moderate, and severe. Specific forms of idiopathic IBD have been further classified by this infiltrate as granulomatous enteritis, eosinophilic enteritis, and lymphoplasmacytic enteritis; there is limited information on microscopic changes with each. Unfortunately, microscopic GI lesions are usually nonspecific, and determination of etiology requires further investigation.

CLAUDIN-3 Protein Expression Relation with Dermatological Diseases: Review Article

Background: When it comes to barrier and pore creation in metazoans, especially vertebrates and tunicates. Claudins are an important family of transmembrane proteins. In epithelia and endothelia's apical junctional complex, chordate claudins are crucial architectural proteins for tight junction strands. Psoriasis patients often have some degree of subclinical intestinal irritation. In gastrointestinal mucosal biopsies, lymphocytic infiltration is found in about 60% of patients. Intestinal absorption is hampered by structural and functional changes in the colon caused by inflammatory cells. Those who have psoriasis have abnormalities in fecal fat excretion, decreased D-xylose absorption, and impaired lactase activity.Objective: To assess the relation between CLAUDIN-3 protein with dermatological diseases. Conclusion: Claudin-3 is a key component of tight junctions, which may serve as marker of gut barrier integrity. Claudin-3 level may be altered in patients with psoriasis.

Endotoxemia in metabolic syndrome and some mechanisms of its development

The aim. Assessment of the relationship between the occurrence of endotoxemia and impaired resorption function of the small intestine, arrhythmia of the motility of the stomach and intestines, and excessive bacterial growth in the metabolic syndrome (MS).Materials and methods. 62 patients with MS were examined. The average age was 48.62+3.75 years. The motor function of the gastrointestinal tract was studied using peripheral electrogastroenterocolography. To assess the absorption processes in the small intestine, stress tests with glucose and d-xylose were used. Blood endotoxin level, quantitative and&amp; qualitative composition of parietal microbiota of small intestine were determined using an Agilent gas chromatograph with mass-selective and flame-ionization detectors (Agilent Technologies, USA).Results. 82.9% of the examined patients with MS showed clinical signs of intestinal damage. The electrical activity of&amp; the&amp; small intestine departments in the postprandial period was low in 70% of patients. The electrical activity of&amp; the&amp; colon on an empty stomach was not changed, and after a food load was reduced. Discoordination of motility is observed between small intestine and the colon, aggravated after food stimulation. A significant decrease in the rhythm of contractions is observed at the frequencies of the jejunum, ileum, and colon both on an empty stomach and in the postprandial period, which indicates a weakening of propulsive bowel contractions in patients with MS. In patients with MS, an increase in&amp; the&amp; absorption of glucose and d-xylose was revealed in comparison with the group of healthy individuals. In patients with MS, excessive bacterial growth in small intestine is observed mainly due to conditionally pathogenic microbiota strains. According to the results of the study of blood endotoxin level in patients with MS, a significant increase was revealed in comparison with the control group. Correlation analysis showed a moderate negative relationship between the level of endotoxin and electrical activity of small intestine, between the level of endotoxin and the ratio of the ratio of&amp; the&amp; colon to the ileum. A moderate positive relationship was established between the degree of endotoxemia increase and glucose absorption in small intestine.Conclusion. A study of the level of endotoxin and indicators of excessive bacterial growth, motor evacuation and resorption functions of small intestine revealed important pathogenetic patterns regarding the contributing role of the latter in&amp; the development of endotoxemia in patients with MS.

A combination of depression and liver Qi stagnation and spleen deficiency syndrome using a rat model.

A syndrome (Zheng in Chinese) plays a critical role in disease identification, diagnosis, and treatment in traditional Chinese medicine (TCM). Clinically, the liver Qi stagnation and spleen deficiency syndrome (LQSSDS) is one of the most common syndrome patterns. Over the past few decades, several animal models have been developed to understand the potential mechanisms of LQSSDS, but until now, simulation of the syndrome is still unclear. Recently, several studies have confirmed that an animal model combining a disease and a syndrome is appropriate for simulating TCM syndromes. Overlapping previous studies have reported that depression is highly associated with LQSSDS; hence, we attempted to develop a rat model combining depression and LQSSDS. We exposed the rats to different durations of chronic unpredictable mild stress (CUMS). Subsequently, the evaluation indicators at macrolevel consisted of behavioral tests including open field test, sucrose preference test, and forced swim test, food intake, body weight, white adipose tissue, fecal water content, visceral hypersensitivity, and small bowel transit, and the evaluation indicators at microlevel included changes of hypothalamic-pituitary-adrenal axis. Serum D-xylose absorption was used to comprehensively confirm and assess whether the model was successful during the CUMS-induced process. The results showed that rats exposed to 6-week CUMS procedure exhibited significantly similar traits to the phenotypes of LQSSDS and depression. This study provided a new rat model for the LQSSDS and could potentially lead to a better understanding of the pathophysiology of LQSSDS and the development of new drugs for this syndrome.

Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway.

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine

BackgroundEnteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption. Material and methodsWild-type C57Bl/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) FL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage. Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05. ResultsVillus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60–360 min after gavage. ConclusionPotentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure.

The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse

BackgroundEnteric serotonin may function as a mucosal growth factor. Previous work demonstrated increased crypt cell proliferation and intestinal mucosal surface area with potentiation of serotonin. While an indirect mechanism was postulated to explain these effects, the presence of 5-HT4 receptors on enterocytes raises the possibility of a direct action of serotonin. We hypothesized that a 5-HT4 specific agonist, prucalopride, would stimulate intestinal mucosal growth and enhance absorptive function in the murine small intestine. MethodsAdult wild-type mice were treated parenterally with prucalopride for 14 days via surgically implanted osmotic pumps. In vivo d-xylose absorption was assessed by oral gavage and serum d-xylose measurements. On day 14, glucose absorption was assessed by instilling a glucose solution into isolated segments of small intestine. The bowel was harvested and examined for morphologic parameters and crypt cell proliferation. ResultsVillus height, crypt depth, and crypt proliferation were significantly increased in the distal small bowel of prucalopride-treated mice compared with control animals. Crypt depth was also increased in the proximal and middle small intestine in treated mice. There was no difference in d-xylose absorption throughout the study period; however, glucose absorption was significantly increased in the distal small intestine of prucalopride-treated mice. ConclusionParenteral administration of the 5-HT4 receptor specific agonist, prucalopride, results in morphologic and functional changes in the murine small intestine that are most prominent in the distal small bowel. While further studies are necessary to delineate the mechanism, it is plausible that the effects are mediated by 5-HT4 receptors on enterocytes.

Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale – A pilot study

Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby compromise absorption of nutrients. To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. Absorption of d-xylose (25g) and zinc (132mg), administered as a single dose, was tested in 14 COPD patients, seven with and seven without cor pulmonale. The presence of cor pulmonale was determined by echocardiography. The concentration of d-xylose and zinc were measured in peripheral blood one, two and three hours after ingestion and used as markers of absorption. Furthermore, urine was collected for five hours to determine the amount of excreted d-xylose. No significant difference in absorption of d-xylose (p=0.28) or zinc (p=0.51) was found between the two groups. However, a trend towards a delay in d-xylose absorption, as assessed by time-to-peak concentration, was observed in patients with cor pulmonale (p=0.08). There was no significant difference in the amount of excreted d-xylose in the urine between the groups (p=0.52). No correlation was found between the tricuspid regurgitation gradient and the absorption of both test-markers (rs=0.34 and rs=-0.25). Likewise, no correlations were found between the inferior caval pressure during the in- and expiration phases and the absorption of d-xylose (rs=-0.09 rs=0.23) or zinc (rs=-0.39, rs=-0.39). We found no indications that small intestinal absorption is affected in a clinically relevant degree in patients with cor pulmonale.

A New Model of Diarrhea with Spleen-Kidney Yang Deficiency Syndrome.

Objective The aim of this study was to examine a new method to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome. Methods A senna leaf (Folium sennae) decoction was made in 3 concentrations of 1.0, 0.5, and 0.25 g/mL. Rats were randomly divided into 4 groups: the control (C)-, high (H)-, middle (M)-, and low (L)- dose groups. The groups received saline, 1.0, 0.5, or 0.25 g/mL senna leaf decoction, respectively, for 4 weeks. Body weight monitoring, food consumption, water intake, defecation frequency, stool Bristol score, weight-loaded forced swimming test, forelimb grip strength test, D-xylose absorption test, serum cortisone, adrenocorticotropic hormone (ACTH), 24 h urine 17-hydroxycorticosteroid (17-OHCS), and histopathological detection were conducted to assess the success of the senna leaf decoction-induced model. Results This study showed that the senna leaf decoction could induce diarrhea and dose-dependently slow body weight growth, reduce food consumption, and increase water intake, stool Bristol score, and defecation frequency. Statistical differences were found between groups H and M in rectal temperature, weight-loaded forced swimming time, forelimb grip strength, and serum cortisone. The D-xylose absorption test also showed dysfunction of intestinal absorption in groups H and M. The serum cortisone and 24 h urine 17-OHCS were significantly reduced in group H. Conclusions Gastric gavage of 10 mL/kg of body weight of a high concentration of a senna leaf decoction (1.0 g/mL) for 4 weeks was used to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome.

Identification of biomarkers in urine of rats with spleen Qi deficiency and biological significance

To identify biomarkers for spleen Qi deficiency by analyzing small molecule metabolites in urine, in order to expound the relationship between biomarkers and metabolic pathways. The spleen Qi deficiency model was established through dietary restriction and overstrain. All of the rats received D-xylose absorption experiment and blood routine test. Urine samples were collected in the next day. The urine samples were analyzed using UPLC-Q-TOF-MS to obtain the dataset of urine metabolic group. Principal component analysis (PCA), orthogonal partialleast squares-discriminant analysis (OPLS-DA) and other multivariate statistical methods were employed to evaluate the quality of the dataset and screen out potential biomarkers of spleen Qi deficiency. The results of D-xylose absorption and blood routine demonstrated that the spleen Qi deficiency model was successfully established. In positive ion mode and negative ion mode, PCA and OPLS-DA score plots could clearly distinguish model group and blank group. According to S-plot of OPLS-DA, VIP value, t-test and area under receiver operating characteristic curve (ROC), 24 biomarkers, including phenylalanine, succinic acid, aconitic acid, isocitrate acid, betaine, kynurenine, indole, creatine, creatinine, orotic acid, xanthine, and xanthurenic acid, were identified as associated with the spleen Qi deficiency, mainly involving energy metabolism, amino acid metabolism, tryptophan metabolism, purine metabolism and pyrimidine metabolism. Urine metabolomics method combined with online software package for data processing and analysis metabolic pathway can provide new methods and ideas for studies for spleen Qi deficiency and other traditional Chinese medicine symptoms.

Increased postprandial glucagon-like peptide-1 (GLP-1) production after endoscopic gastrointestinal bypass using the Cousin lumen-apposing stent in a porcine model.

EGIA was technically successful with no complications observed during clinical monitoring. Endoscopic and postmortem examinations during the second part of study showed a secure anastomosis between the stomach and the intestinal limb in all except one minipig. Both minipigs subjected to EGIA and those in the control group (OGIA) exhibited increased postprandial glucagon-like peptide-1 (GLP-1) production (incretin secretion) and impaired D-xylose absorption (malabsorption effect). CONCLUSION : Performing EGIA with this dedicated stent appears safe, technically feasible, durable, and reproducible in providing a simple and effective endoscopic GI bypass capable of ensuring metabolic effect.

Iraqi Propolis effective in avoiding deviations of gut rat's homeostasis exposed to AFB-1

Background: Consumption of food contaminated with Aflatoxin-B1(AF-B1), caused deleterious effects on different body’s systems ,specially GIT in direct and indirect manners. To investigate the protective role of propolis against AF-B1 effects on rats gut, 24 male rats divided into equal 4 groups: group (C )was control, second group (AF) received Aflatoxin-B1 ( 0.025mg/kg ), third group( P) received Propolis in dose (50 mg /kg BW) and the fourth group( AFP) received Aflatoxin-B1 (0.025 mg/ 1kg BW) + Propolis (50 mg / 1kg BW).after 60 days of experiment , intestinal D-zylose adsorption and histomorphological changes were measured&#x0D; Results: Results revealed that intestinal absorption function of D-Xylose sugar was reduced in AFB-1 exposed rats , meanwhile Propolis improve D-xylose absorption in rats exposed to the AFB-1. Histomorphological measurements include mucosa thickness, Villus high, Crypts depth, Villus/crypt ratio, and goblet cells density in the three portions of small intestine decreased significantly in AF group and increased significantly in P group and kept semi-normal in AFP group in comparison with the control group. Analysis of light microscopic photograph revealed that administration of aflatoxin-B1 cause deleterious changes in stomach, and intestinal tissues, while Propolis was efficient in improving these changes to normal condition.&#x0D; Conclusions: Intestinal absorptive function and histomorphological measurements were altered by Aflatoxin-B1, and the duodenum was the most affected part from the intestine. Results of propolis showed a high activity to improve all the above measurements and counter the deleterious effect of Aflatoxin-B1 to normal situation.