small intestinal transit
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2021 ◽  
Author(s):  
Feng Ye ◽  
Jian Zhang ◽  
Yi-long Wang ◽  
Shu-mei Lin ◽  
Xi Zhang ◽  
...  

Abstract BackgroundAcute-on-chronic liver failure (ACLF) has a high risk of mortality in liver diseases without effective treatment. Xiao Chai Hu decoction (XCHD) is a traditional herbal formula, widely administered for liver disease, including anti-hepatic fibrosis and anti-inflammatory. MethodsTo investigate whether XCHD prevents the progression of ACLF and the underlying mechanisms. Methods: Sprague–Dawley rats with compound factors were randomly divided into model control group with 30 rats and four treatment groups with 20 rats in each group: Polyene phosphatidylcholine (100 mg/kg; PP) group; high dose (44.5 g/kg; HXCHD), middle dose (26.5 g/kg; MXCHD), and low dose (8.5 g/kg; LXCHD). Firstly, liver disease progression after XCHD treatment was measured by detecting: 1) the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), and albumin, prothrombin time (PT); 2) the survival rate and rat-adapted model for end-stage liver disease (MELD) score; 3) the hepatic hyperplastic collagen fibers with Masson’s trichrome staining; 4) the serum level of TNF-α and endotoxin induced hepatocyte apoptosis expression; 5) the ileum slow waves, gastric emptying, and small intestinal transit after XCHD treatment. ResultsThe XCHD groups showed improved serum biochemical hepatic parameters, histological liver changes, and survival rate. In addition, the XCHD treatment decreased the serum level of TNF-α and endotoxin and reduced hepatocyte apoptosis. XCHD decreased the normal percentage ileum slow waves, prolonged gastric emptying, and increased the small intestinal transit of ACLF. ConclusionsXCHD prevented the progression of ACLF partially via the prokinetic effects on gastrointestinal motility to reduce TNF-α, endotoxin, and hepatocyte apoptosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuchi Zhang ◽  
Xuan Han ◽  
Zhuoqun Li ◽  
Yu Zhang ◽  
Lihong Liang ◽  
...  

Abstract Background Irreversible electroporation (IRE) is an emerging tissue ablation technique with widespread potential, especially for cancer treatment. Although the safety and efficacy of IRE for gastric tissue ablation have been demonstrated, there is a gap of knowledge regarding the effect of electroporation pulse (EP) on the physiology and histopathology of the stomach. This study applied EP to the stomach of healthy rats and investigated the digestive function, serum marker levels, and gastric tissue structure of EP-treated rats. Methods Ninety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulse (500 V, 99 pluses, 1 Hz, 100 µs) was delivered to the stomachs of rats using a tweezer-style round electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate the digestive function. Serum marker levels were determined using ELISA. Haematoxylin–eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis. Results No  significant effect on gastric emptying or secretion was found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, serum TNF-α and IL-1β levels temporarily changed during the acute phase but returned to baseline within 28 days. Moreover, histopathological analysis revealed that cell death occurred immediately post-EP in the ablation area, whereas the gastric wall scaffold in the ablation region remained intact post-EP. Conclusions This study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for more comprehensive applications of this technique.


2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Vishwas Mishra ◽  
Avipsa Bose ◽  
Shashi Kiran ◽  
Sanghita Banerjee ◽  
Idrees A. Shah ◽  
...  

Activating mutations in receptor guanylyl cyclase C (GC-C), the target of gastrointestinal peptide hormones guanylin and uroguanylin, and bacterial heat-stable enterotoxins cause early-onset diarrhea and chronic inflammatory bowel disease (IBD). GC-C regulates ion and fluid secretion in the gut via cGMP production and activation of cGMP-dependent protein kinase II. We characterize a novel mouse model harboring an activating mutation in Gucy2c equivalent to that seen in an affected Norwegian family. Mutant mice demonstrated elevated intestinal cGMP levels and enhanced fecal water and sodium content. Basal and linaclotide-mediated small intestinal transit was higher in mutant mice, and they were more susceptible to DSS-induced colitis. Fecal microbiome and gene expression analyses of colonic tissue revealed dysbiosis, up-regulation of IFN-stimulated genes, and misregulation of genes associated with human IBD and animal models of colitis. This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2826
Author(s):  
Malcolm J. Borg ◽  
Cong Xie ◽  
Christopher K. Rayner ◽  
Michael Horowitz ◽  
Karen L. Jones ◽  
...  

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 759
Author(s):  
Alice Melocchi ◽  
Marco Uboldi ◽  
Francesco Briatico-Vangosa ◽  
Saliha Moutaharrik ◽  
Matteo Cerea ◽  
...  

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.


Author(s):  
Vijay L. Kumar ◽  
Abhimanu Pandey ◽  
Hilal Ahmad

Abstract Objectives Roxithromycin, a macrolide antibiotic, has been shown to ameliorate acetic acid induced colitis in rats by suppressing inflammation and oxidative stress. The aim of this study was to evaluate the effect of roxithromycin on small intestinal transit and cholinergic responsiveness of the colonic smooth muscles of colitic rats. Methods Colitis was induced in rats by acetic acid and the small intestinal transit was determined by measuring the distance traversed by charcoal meal from the gastro-duodenal junction in 1 h. The test drug roxithromycin, reference drug mesalazine and anti-inflammatory drug diclofenac were administered orally before inducing colitis and their effect on intestinal transit was compared with colitic control group. The effect on cholinergic responsiveness of colonic smooth muscles was evaluated in vitro by plotting a dose-response curve using different concentrations of acetylcholine. The concentration producing 50% of maximal response (EC50) was calculated for all the treatment groups. Results The small intestinal transit was enhanced in colitic rats as compared to normal rats (86.00 ± 1.36 vs. 57.00 ± 1.34 cm; p<0.001). Like mesalazine, roxithromycin normalized intestinal transit while diclofenac was ineffective. The results of in vitro experiment show that colitis increased cholinergic responsiveness of the colonic smooth muscles that was not affected by roxithromycin and mesalazine while diclofenac significantly decreased it. Conclusions This study shows that like mesalazine, roxithromycin affords protection in colitis mainly by normalizing propulsive movement of the small intestine than by affecting cholinergic responsiveness of the colonic smooth muscles.


Author(s):  
EL-Akhal Jamila ◽  
Chda Alae ◽  
Tazi Abdelali ◽  
Boukir Abdelatif ◽  
Bencheikh Rachid

Objective: The aim of this present study is to investigate the antidiarrheal, spasmolytic and antioxidant activities of aqueous extract of Mentha suaveolens Ehrh (AEMS), to study their underlying mechanisms in animal models and to reveal its main functional groups using Fourier Transform Infra-Red Spectroscopy (FTIR). Methods: Mentha suaveolens Ehrh was studied for antidiarrheal activity on Wistar rats of both sexes at the doses of 200 and 800 mg/kg body weight using castor oil-induced diarrhea, castor oil-induced enteropooling and small intestinal transit models. The extract was studied for antispasmodic property in isolated rabbit jejunum using various spasmogenic agents including Ach (10-5M), KCl (100 mM) and in the absence and in the presence of L-NAME (10-4 M) and the methylene blue (10-5 M).The antioxidant capacity of AEMS was carried out using DPPH radical scavenging activity and the ferric reducing antioxidant potential (FRAP). Ascorbic acid and Butylated HydroxyToluene (BHT) were used as references. The functional chemical groups were determined by FTIR. Results: The great antidiarrheal potential of AEMS seems to be mediated through calcium antagonism. The marked and concentration-dependent induced spasmolytic effect of AEMS appears to involve Ca2+ voltage channel blockade and the NO/cGMP pathway activation. AEMS possessed strong and concentration-dependent antioxidant potency using DPPH and FRAP. Polyphenols, carboxyl and carbohydrates were found to be the main functional groups in the AEMS analyzed by FTIR. Conclusion: Overall, our current findings provide scientific proves in animal models for the traditional use of AEMS in folk medicine for the prevention or the treatment of gastrointestinal diseases in Morocco.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Chinedu Nwuke ◽  
Bartholomew Ibeh

Aim: The study investigated the antidiarrheal potential of methanol extract of Combretum dolichopetalum and its solvent fractions. Method: Leaves of Combretum dolichopetalum were extracted using methanol as solvent. This was classified as the crude methanol extract (MECD). The crude extract was further fractionated using column chromatographic techniques to get various fractions. Castor oil was used to induce diarrhea in the animals, following atropine and the plant extracts to confirm any antidiarrheal activity. Fecal excretion and absorption/secretion ratio, enteropooling, small intestinal transit, glucose estimation, free fatty acid estimation and fecal osmolarity were employed to serve as antidiarrheal biomarker. Result: result showed improvements in all studied biomarkers compared to the negative control. The extract worked similarly like the standard drug used atropine. Conclusion: From the result of this study, it can be concluded that the methanol extract of Combretum dolichopetalum and it fractions contains compounds with antidiarrheal potentials, and this justifies it use in ethnomedicine.


Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1438
Author(s):  
Helen H. Wang ◽  
Piero Portincasa ◽  
Min Liu ◽  
Patrick Tso ◽  
David Q.-H. Wang

The cholecystokinin A receptor (CCKAR) is expressed predominantly in the gallbladder and small intestine in the digestive system, where it is responsible for CCK’s regulation of gallbladder and small intestinal motility. The effect of CCKAR on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. The CCKAR gene has been identified to be an important gallstone gene, Lith13, in inbred mice by a powerful quantitative trait locus analysis. Knockout of the CCKAR gene in mice enhances cholesterol cholelithogenesis by impairing gallbladder contraction and emptying, promoting cholesterol crystallization and crystal growth, and increasing intestinal cholesterol absorption. Clinical and epidemiological studies have demonstrated that several variants in the CCKAR gene are associated with increased prevalence of cholesterol cholelithiasis in humans. Dysfunctional gallbladder emptying in response to exogenously administered CCK-8 is often found in patients with cholesterol gallstones, and patients with pigment gallstones display an intermediate degree of gallbladder motility defect. Gallbladder hypomotility is also revealed in some subjects without gallstones under several conditions: pregnancy, total parenteral nutrition, celiac disease, oral contraceptives and conjugated estrogens, obesity, diabetes, the metabolic syndrome, and administration of CCKAR antagonists. The physical–chemical, genetic, and molecular studies of Lith13 show that dysfunctional CCKAR enhances susceptibility to cholesterol gallstones through two primary mechanisms: impaired gallbladder emptying is a key risk factor for the development of gallbladder hypomotility, biliary sludge (the precursor of gallstones), and microlithiasis, as well as delayed small intestinal transit augments cholesterol absorption as a major source for the hepatic hypersecretion of biliary cholesterol and for the accumulation of excess cholesterol in the gallbladder wall that further worsens impaired gallbladder motor function. If these two defects in the gallbladder and small intestine could be prevented by the potent CCKAR agonists, the risk of developing cholesterol gallstones could be dramatically reduced.


2020 ◽  
Author(s):  
Yuchi Zhang ◽  
Xuan Han ◽  
Zhuoqun Li ◽  
Yu Zhang ◽  
Lihong Liang ◽  
...  

Abstract BackgroundElectroporation pulse (EP) is an emerging tissue ablation technique with widespread potential, including in the treatment of multiple cancer types. However, there is a lack of knowledge about its effect on the physiology and histopathology of stomachs. The aim of this study was to investigate biological effects of EP applied to stomachs of healthy rats on digestive function, serum marker levels, and gastric tissue structure.MethodsNinety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulses (500 V, 99 pluses, 1 Hz, 100 μs) was delivered to the stomachs of the rats using a forceps electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate digestive function. Levels of serum markers were determined using ELISA. Haematoxylin–eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis.ResultsNo significant effect on gastric emptying or secretion were found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, levels of serum markers such as TNF-α and IL-1β changed temporarily in the acute term but soon returned to normal within 28 days. Moreover, histopathological analysis revealed that that the cell death in ablation area occurred immediately post-EP, and the gastric wall scaffold in the ablation region remained intact post-EP.ConclusionsThis study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for the wider use of this technique in future studies.


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