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Food & Function Oct 2020The prebiotics inulin (INU) and isomalto-oligosaccharide (IMO) influence intestinal health and immunity, but their effects on constipation are not clearly established....
Effects of inulin and isomalto-oligosaccharide on diphenoxylate-induced constipation, gastrointestinal motility-related hormones, short-chain fatty acids, and the intestinal flora in rats.
The prebiotics inulin (INU) and isomalto-oligosaccharide (IMO) influence intestinal health and immunity, but their effects on constipation are not clearly established. We evaluated the effects of INU and IMO in a rat model of diphenoxylate-induced constipation. Twenty-four male rats were divided into four groups: basal diet (Con), 40 mg kg-1 diphenoxylate (PCon), 20 g kg-1 INU and treated with 40 mg kg-1 diphenoxylate, and 20 g kg-1 IMO and treated with 40 mg kg-1 diphenoxylate. INU and IMO increased the number, weight, and water content of fecal pellets, and decreased the time to the first black stool in rats with constipation. Serum levels of the gastrointestinal motility-related hormones adrenocorticotropic hormone (ACTH), motilin (MTL), and Substance P (SP) were higher and corticosterone (CORT), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were lower in rats treated with prebiotics than in untreated rats. Colon tissue levels of MTL and SP were increased, and VIP and CGRP were decreased by prebiotics. Furthermore, in rats with constipation, INU and IMO increased the colonic contents of short-chain fatty acids. The relative abundance of Bacteroidetes was lower in the prebiotics groups than in the Con and PCon groups. Lactobacillus was more abundant in the INU and IMO groups than in PCon rats. Lactobacillus reuteri and Lactobacillus intestinalis were more abundant in the IMO group than in the PCon group (P < 0.01), and L. intestinalis was more abundant in the INU group than in the PCon group (P < 0.01). In summary, INU and IMO improved constipation and altered the intestinal microbiota in a rat model of constipation.
Topics: Animals; Bacteria; Constipation; Diphenoxylate; Fatty Acids, Volatile; Feces; Gastrointestinal Hormones; Gastrointestinal Microbiome; Gastrointestinal Motility; Humans; Intestines; Inulin; Male; Oligosaccharides; Prebiotics; Rats
PubMed: 33030479
DOI: 10.1039/d0fo00865f -
Evidence-based Complementary and... 2020Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the...
BACKGROUND
Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the downregulation of AQP3 can regulate liquid water metabolism and intestinal permeability in irritable bowel syndrome (IBS) rats' colon via NF-B pathway. In this study, we investigated whether the laxative effect of Maren pills is associated with the regulation of AQP3 and NF-B signaling pathway in the colon.
METHODS
The compound diphenoxylate suspension-induced STC rats received Maren pills intragastrically for 1 consecutive week to evaluate the laxative effect of Maren pills involving the regulation of AQP3 and NF-B signaling pathway. Moreover, human intestinal epithelial cells (HT-29) were treated with drug serum to obtain in vitro data.
RESULTS
Our results revealed that treatment with Maren pills increased the stool number, moisture content of feces, and intestinal transit rate in a dose-dependent manner. Maren pills significantly increased the AQP3, fibrosis transmembrane conductance regulator (CFTR), and protein kinase A (PKA) proteins in the colon of rats and in HT-29 cells. Mechanistically, Maren pills obviously inhibited the activation of NF-B pathway in the colon of rats and in HT-29 cells.
CONCLUSION
These results suggest that the laxative effect of Maren pills is associated with the increased expression of AQP3 by downregulating NF-B signal pathway.
PubMed: 32774435
DOI: 10.1155/2020/9837384 -
Journal of Agricultural and Food... Jul 2020Three new flavonoids, quercetin-3--6-[methyl-()-3-hydroxy-3-methylglutaroyl(1→6]-β-d-glucopyranoside (),...
Three new flavonoids, quercetin-3--6-[methyl-()-3-hydroxy-3-methylglutaroyl(1→6]-β-d-glucopyranoside (), kaempferol-3--[methyl-()-3-hydroxy-3-methylglutaroyl(1→6)]-β-d-glucopyranoside (), and quercetin-3--6-[()-4-methoxy-5-methylhexa-2,4-dienoatyl(1→6)]-β-d-glucopyranoside (), and two new alkaloids, 5-dehydroxymethyl-pyrrolemarumine 4″--α-l-rhamnopyranoside () and -methyl--((4--α-l-rhamnopyranoside)benzyl) oxalamide (), together with 45 known compounds (-) were isolated from the leaves of Lam. Among those compounds, 1-octacosanol (), a straight-chain 28-carbon alcohol, exhibited good activity against diphenoxylate-induced constipation in mice, which is obtained as a laxative constituent from the plant for the first time. In order to have an accurate understanding of the content of compound , a quantification with gas chromatography-tandem mass spectrometry (GC-MS/MS) was carried out. The anti-inflammatory and α-glucosidase inhibitory activity of some compounds also was assessed.
Topics: Flavonoids; Gas Chromatography-Mass Spectrometry; Laxatives; Moringa oleifera; Plant Extracts; Plant Leaves
PubMed: 32631058
DOI: 10.1021/acs.jafc.0c01564 -
Laxative Effects of Yangyin Tongmi Capsule on a Model of Diphenoxylate-Induced Constipation in Mice.Evidence-based Complementary and... 2020Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is...
Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is used in the treatment of constipation, while the underlying mechanisms remain unknown. Herein, this work attempted to prove the effects of YTC on constipation treatment and its possible mechanisms. KM mice were randomly divided into four groups ( = 10/group) and treated with double distilled water (Control), diphenoxylate (Model: 10 mg/kg), or diphenoxylate plus low-dose YTC (L-YTC: 0.6 g/kg) or high-dose YTC (H-YTC: 1.2 g/kg). The data indicated that YTC can significantly shorten the discharge time of the first black stool, improve intestinal propulsion rate, and increase the water content and quantity of feces in mice. ELISA suggested that YTC regulate the content of intestinal hormones and neurotransmitters, such as motilin (MTL), gastrin (GT), somatostatin (SST), substance P (SP), acetylcholine (Ach), and nitric oxide (NO). The expression levels of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) in the colon were examined by immunohistochemistry. In the meantime, the expression levels of P2X2, C-kit, and stem cell factor (SCF) in the colon were examined by western blot analysis. The results of this study suggest that YTC has mitigative effects on diphenoxylate-induced constipation by regulating the content of intestinal hormones and neurotransmitters and regulating the expression of related proteins in the colon.
PubMed: 32148532
DOI: 10.1155/2020/1471824 -
Cureus Oct 2019Diphenoxylate-atropine (Lomotil) intoxication incidence was significantly high in the past, but seeing such cases in the present day of modern and advanced medicine,...
Diphenoxylate-atropine (Lomotil) intoxication incidence was significantly high in the past, but seeing such cases in the present day of modern and advanced medicine, hints about the gaps in the practice of medicine. In our case, a general physician maltreated an infant for diarrhea with an adult dose of diphenoxylate-atropine (Lomotil), a Food and Drug Administration (FDA) unapproved drug, which caused labored breathing and pinpoint pupils. After being maltreated, at the time of presentation to the emergency room (ER), she was being misdiagnosed as a case of dehydration until doctors noticed miosis and reached the diagnosis of diphenoxylate-atropine (Lomotil) toxicity. Her condition completely reversed with a single dose of naloxone. Hence, this case highlights the need for basic knowledge about the dosage of drugs for different age groups, especially infants, along with the importance of adherence to the evaluation protocols for accurate management.
PubMed: 31763098
DOI: 10.7759/cureus.5875 -
Drug, Healthcare and Patient Safety 2019The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the...
BACKGROUND
The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the FDA through the MedWatch program. A significant number of adverse events reported in the FAERS database have been for opioid use. The objective of this study was to determine the frequency counts and associated deaths of opioid drug names in the FAERS database.
METHODS
Drug data were obtained from the DRUG and OUTCOME files in the database. Drugs identified included: morphine, fentanyl, oxycodone, hydrocodone, tramadol, hydromorphone, methadone, codeine, oxymorphone, meperidine, propoxyphene, diphenoxylate, and heroin. Frequency counts and concomitant deaths of opioid drug names were determined via the MySQL database management system.
RESULTS
Fifteen different opioid drugs identified in the FAERS database were associated with ADEs, including death, and 3 drugs (oxycodone, hydrocodone, fentanyl) accounted for more than half of the reports. The highest frequency count value was 158,181 for oxycodone, which represents approximately 20.2% of the frequency counts for the opioids. The lowest frequency count value was 2,161 for dextromethorphan, which represents approximately 0.3% of the total. The opioid with the highest proportion of deaths to drug count was heroin (71.8%), followed by dextromethorphan (55.6%), methadone (37.2%), morphine (26.8%), and propoxyphene (23.7%).
CONCLUSION
The FAERS database represents an important source for detection and reporting of adverse drug events (ADEs), in particular the opioids and related drugs. It remains a challenge to estimate the true incidence of ADEs for this class of drugs in the general population.
PubMed: 31695510
DOI: 10.2147/DHPS.S214771 -
Bioinformatics and Biology Insights 2019Diarrhoeal disease kills about 1.5 million human beings per year across the continents. The enterotoxigenic (ETEC) pathotype has been noted as a major cause of...
Diarrhoeal disease kills about 1.5 million human beings per year across the continents. The enterotoxigenic (ETEC) pathotype has been noted as a major cause of diarrheal disease in human and livestock. The aim of this study is to identify broad-spectrum molecular targets in bacteria and broad-spectrum lead compounds (functional inhibitors) with high efficacy and no significant adverse implication on human systems, in relevance to diarrhea therapy through computational approaches which include phylogenetics, target prediction, molecular docking, and molecular flexibility dynamic simulations. Three molecular target genes, , and , which code for uridine diphosphate--acetylglucosamine-1-carboxyvinyltransferase, 1-deoxy-D-xylulose-5-phosphate reductoisomerase, and deoxyribonucleic acid polymerase III alpha subunit, respectively, were found to be highly conserved in 7 diarrhea-causing microbes. In addition, 21 potential compounds identified showed varied degree of affinity to these enzymes. At free energy cutoff of -8.0 kcal/mol, the highest effective molecular target was DNA polymerase III alpha subunit (PDB ID: 4JOM) followed by UDP--acetylglucosamine-1-carboxyvinyltransferase (PDB ID: 5UJS), and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PDB ID: 1ONN), while the highest effective lead compound was -coeleneterazine followed by amphotericin B, MMV010576, MMV687800, MMV028694, azithromycin, and diphenoxylate. The flexibility dynamics of DNA polymerase III alpha subunit unraveled the atomic fluctuation which potentially implicated Asp593 as unstable active site amino acid residue. In conclusion, bacteria gene or its protein is a highly promising molecular target for the next generation of antibacterial drugs of the class of -coeleneterazine.
PubMed: 31695343
DOI: 10.1177/1177932219884297 -
The Manufacturing Process of Kiwifruit Fruit Powder with High Dietary Fiber and Its Laxative Effect.Molecules (Basel, Switzerland) Oct 2019Kiwifruit is rich in vitamins, minerals, dietary fiber and other functional components, and it has long been used as a functional food to treat intestinal ailments such...
Kiwifruit is rich in vitamins, minerals, dietary fiber and other functional components, and it has long been used as a functional food to treat intestinal ailments such as constipation. The current research made full use of the kiwifruit, the juice was prepared by microencapsulation, and the dietary fiber in kiwifruit pomace was modified by enzymatic hydrolysis and grinding, then, the two were mixed to obtain an ultra-micro kiwifruit powder (UKP). In addition, the laxative effect of the UKP was verified by a diphenoxylate induced constipated mice model. The results demonstrated that compared with the raw samples, the retention rate of vitamin C, lutein and catechin in UKP were 83.3%, 81.9% and 88.3%, respectively, thus effectively avoiding the loss of functional components during the processing of kiwifruit. Moreover, α-amylase, protease and the ball milling process effectively reduced the size of dietary fiber in kiwifruit pomace, and its water-holding capacity (WHC), oil-holding capacity (OHC) and swelling capacity (SWC) were enhanced by 1.26, 1.65 and 1.10 times, respectively. Furthermore, to analyze the laxative effect of the UKP, a constipation mice model was established by diphenoxylate treatment (5 mg·kg, i.g.) for the last week, with or without UKP supplementation (2.4 g·kg B.W. per day) for 4 weeks. The results demonstrated that UKP significantly increased feces condition (fecal output and dejecta moisture content, gut transit (the intestinal propulsion rates) and substance P (SP) levels in portal vein plasma, and it decreased the whole gut transit time and mucinogen granules secreted by goblet cell in constipated mice.
Topics: Actinidia; Animals; Constipation; Dietary Fiber; Fruit; Laxatives; Male; Mice; Plant Extracts
PubMed: 31652679
DOI: 10.3390/molecules24213813 -
The Journal of Trauma and Acute Care... Oct 2019Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A...
Antimotility agents for the treatment of acute noninfectious diarrhea in critically ill patients: A practice management guideline from the Eastern Association for the Surgery of Trauma.
BACKGROUND
Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice.
METHODS
The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay.
RESULTS
The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found.
CONCLUSION
Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea.
LEVEL OF EVIDENCE
Systematic Review/Guidelines, level III.
Topics: Adult; Antidiarrheals; Critical Illness; Diarrhea; Diet Therapy; Diphenoxylate; Gastrointestinal Motility; Humans; Loperamide; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31574060
DOI: 10.1097/TA.0000000000002449 -
Digestive Diseases and Sciences Dec 2019
Review
Topics: Antidiarrheals; Autonomic Nervous System Diseases; Blind Loop Syndrome; Celiac Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diagnosis, Differential; Diarrhea; Diphenoxylate; Enteric Nervous System; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Gastrointestinal Motility; Hypoglycemic Agents; Imidazoles; Inflammation; Inflammatory Bowel Diseases; Interstitial Cells of Cajal; Intestinal Absorption; Intestinal Mucosa; Irritable Bowel Syndrome; Loperamide; Neuroglia; Non-Nutritive Sweeteners; Oxidative Stress; Phenylalanine; Serotonin 5-HT3 Receptor Antagonists
PubMed: 31541370
DOI: 10.1007/s10620-019-05846-6