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Cureus Apr 2023A high volume of ileostomy output in patients with extensive bowel resection can be hard to manage. This leads to extensive loss of fluids and electrolytes along with...
A high volume of ileostomy output in patients with extensive bowel resection can be hard to manage. This leads to extensive loss of fluids and electrolytes along with malabsorption. Medications have traditionally controlled it by delaying intestinal transit and decreasing intestinal and gastric secretion using opiates, loperamide, diphenoxylate, omeprazole, somatostatin, and octreotide. However, many patients depend on parenteral nutrition and fluid and electrolyte infusions, even with optimal drug therapy. Despite the best possible care, they may develop renal failure. Teduglutide is a glucagon-like peptide-2 (GLP-2) analog given as a daily subcutaneous injection, and it has been promising in managing short bowel syndrome. It has been effective in decreasing the dependence on parenteral nutrition. However, improving fluid and electrolyte balance can precipitate cardiac failure in some patients, especially those with borderline cardiac functions, hypertension, and thyroid disorders. This usually presents in the first few months of the initiation of teduglutide therapy and may require stopping the medication. We present the case report of an elderly female with a high-output stoma on parenteral nutrition on teduglutide. There was a significant decrease in stoma output, and parenteral nutritional support could be stopped. However, she presented with worsening dyspnea and was diagnosed with cardiac failure with an ejection fraction of 16%-20%. The baseline ejection fraction was 45%, done six months before this. Coronary angiography showed no stenosis in any vessels, and the decline in left ventricular ejection fraction and fluid overload was attributed to teduglutide therapy.
PubMed: 37197113
DOI: 10.7759/cureus.37518 -
Journal of Clinical Medicine Mar 2023In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid... (Review)
Review
In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.
PubMed: 37048572
DOI: 10.3390/jcm12072488 -
Chinese Journal of Integrative Medicine May 2023To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
OBJECTIVE
To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).
METHODS
According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.
RESULTS
EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.
CONCLUSION
EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Topics: Mice; Animals; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Electroacupuncture; Beclin-1; Signal Transduction; Constipation; TOR Serine-Threonine Kinases; Autophagy; Neuroglia; Mammals
PubMed: 36973529
DOI: 10.1007/s11655-023-3594-3 -
Biomedicine & Pharmacotherapy =... May 2023Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which...
Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.
Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.
Topics: Animals; Mice; Constipation; Inflammation; Intestines; NF-kappa B; Signal Transduction; AMP-Activated Protein Kinases
PubMed: 36906969
DOI: 10.1016/j.biopha.2023.114495 -
Cureus Feb 2023The clinical course of a patient with chemotherapy-related diarrhea (CRD) refractory to standard therapy was monitored over the course of 21 days. The patient was...
The clinical course of a patient with chemotherapy-related diarrhea (CRD) refractory to standard therapy was monitored over the course of 21 days. The patient was minimally responsive to traditional treatment options, including bismuth subsalicylate, diphenoxylate-atropine, loperamide, octreotide, and oral (PO) steroids, and exhibited reportable improvements with the addition of intravenous (IV) methylprednisolone to other antidiarrheal agents. We present a case of CRD in an 82-year-old female. She was initiated on chemotherapy three weeks prior and has experienced severe diarrhea since her initiation. Despite the use of first-line antidiarrheal therapies, including loperamide, diphenoxylate-atropine, and octreotide, both subcutaneously and via continuous infusion drip, no infectious cause was found. She also received the non-absorbing corticosteroid budesonide, but her diarrhea persisted. After experiencing severe hypotension and hypovolemia secondary to profuse diarrhea, she was placed on IV steroids, which quickly reduced her symptoms. The patient was then transitioned to oral steroids and discharged on a tapering regimen. We recommend using IV steroids to treat CRD if first-line therapies fail. Utilizing IV steroids efficiently and effectively can decrease the symptoms of persistent diarrhea and lead to rapid recovery.
PubMed: 36895532
DOI: 10.7759/cureus.34634 -
Frontiers in Nutrition 2022Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or...
INTRODUCTION
Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or combined on diphenoxylate-induced constipation and explore the underlying mechanisms using a mouse model.
METHODS
ICR mice were randomly divided into five groups. The normal and constipation model groups were intragastrically administrated with PBS. The ST, , and synbiotic groups were intragastrically administrated with ST (1.5 g/kg body weight), alive (3 × 10 CFU/mouse), or ST + (1.5 g/kg plus 3 × 10 CFU/mouse), respectively. After 21 days of intervention, all mice except the normal mice were intragastrically administrated with diphenoxylate (10 mg/kg body weight). Defecation indexes, constipation-related intestinal factors, serum neurotransmitters, hormone levels, short-chain fatty acids (SCFAs), and intestinal microbiota were measured.
RESULTS
Our results showed that three interventions with ST, , and synbiotic combination (ST + . sakei) all alleviated constipation, and synbiotic intervention was superior to ST or alone in some defecation indicators. The RT-PCR and immunohistochemical experiment showed that all three interventions relieved constipation by affecting aquaporins (AQP4 and AQP8), interstitial cells of Cajal (SCF and c-Kit), glial cell-derived neurotrophic factor (GDNF), and Nitric Oxide Synthase (NOS). The three interventions exhibited a different ability to increase the serum excitatory neurotransmitters and hormones (5-hydroxytryptamine, substance P, motilin), and reduce the serum inhibitory neurotransmitters (vasoactive intestinal peptide, endothelin). The result of 16S rDNA sequencing of feces showed that synbiotic intervention significantly increased the relative abundance of beneficial bacteria such as , and regulated the gut microbes of STC mice. In conclusion, oral administration of ST or alone or combined are all effective to relieve constipation and the symbiotic use may have a promising preventive effect on STC.
PubMed: 36687730
DOI: 10.3389/fnut.2022.1039403 -
Frontiers in Pharmacology 2022Constipation is a common syndrome and a worldwide healthy problem. Constipation patients are becoming younger, with a 29.6% overall prevalence in children, which has...
Constipation is a common syndrome and a worldwide healthy problem. Constipation patients are becoming younger, with a 29.6% overall prevalence in children, which has captured significant attention because of its epigenetic rejuvenation and recurrent episodes. Despite the usage of rhubarb extract to relieve constipation, novel targets and genes implicated in target-relevant pathways with remarkable functionalities should still be sought for. We established a reliable constipation model in C57B/6N male mice using intragastric administration diphenoxylate, and the eligible subjects received 600 mg/25 g rhubarb extract to alleviate constipation. Resultant constipation was morphological and genetically compared with the specimen from different groups. Constipation mice exhibited thicker muscle layers, higher levels of cytokines, including IL-17 and IL-23, and lower content of IL-22. Bacterial abundance and diversity varied tremendously. Notably, the alterations were reversed following rhubarb extract treatment. Additionally, Constipation also had a substantial impact on short-chain fatty acids (SCFAs), medium- and long-chain fatty acids (MLCFAs), and the expression of SCFA receptors, GPR41 and GPR43. This thesis has provided insight that rhubarb extract promoted the flexibility of collagen fiber, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokines, and maintained gut microflora balance with potential impacts on the fatty acid and polyamine metabolism.
PubMed: 36545319
DOI: 10.3389/fphar.2022.1048134 -
World Journal of Gastroenterology Sep 2022Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and...
BACKGROUND
Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear.
AIM
To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods.
METHODS
STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence.
RESULTS
JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis.
CONCLUSION
This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.
Topics: Acetylcholine; Animals; Apoptosis; Constipation; Diphenoxylate; Gastrointestinal Transit; Mice; Neuroglia; Proto-Oncogene Proteins c-akt; Quercetin; Taurine
PubMed: 36160643
DOI: 10.3748/wjg.v28.i34.5007 -
Frontiers in Nutrition 2022Foxtail millet () has a long history of treating gastrointestinal ailments in China; however, little is known about the functional mechanism driving its therapeutic...
Foxtail millet () has a long history of treating gastrointestinal ailments in China; however, little is known about the functional mechanism driving its therapeutic effects. The primary edible form of millet is porridge. This study investigates the effects of millet porridge on diphenoxylate-induced constipation and intestinal microflora in mice. Fifty mice were randomly divided into five groups: normal control group, constipation model group, and low-dose, medium-dose, and high-dose millet porridge groups. After 14 days of millet porridge gavage, constipation was induced and measured. The results showed that millet porridge prevented constipation by increasing the water content of feces, shortened the time of the first melena defecation, promoted gastric emptying, and improved the rate of gastrointestinal propulsion. Millet porridge also dose-dependently increased levels of and and decreased levels of , , and in the intestine. These results show that millet porridge could accelerate intestinal motility and change the proportions of intestinal flora and that it has a potent prebiotic effect.
PubMed: 36071942
DOI: 10.3389/fnut.2022.965687 -
Zhen Ci Yan Jiu = Acupuncture Research Aug 2022To observe the effect of electroacupuncture (EA) of bilateral "Tianshu"(ST25) at different frequencies on the first black stool discharge time, colonic electromyography...
[Effect of electroacupuncture of "Tianshu"(ST25) at different frequencies on electromyography and immunoactivity of SP and VIP of colon in rats with slow transit constipation].
OBJECTIVE
To observe the effect of electroacupuncture (EA) of bilateral "Tianshu"(ST25) at different frequencies on the first black stool discharge time, colonic electromyography (EMG) and immunoactivity of vasoactive intestinal peptide (VIP) and substance P (SP) in the colon tissue in rats with slow transit constipation (STC), so as to choose a better stimulating frequency in the treatment of STC.
METHODS
A total of 50 male Wistar rats were randomized into control, model, 2 Hz-EA, 100 Hz- EA, and 2 Hz/100 Hz-EA groups, with 10 rats in each group. The STC model was established by intraperitoneal injection of compound diphenoxylate suspension fluid (10 mg/kg). EA was applied to bilateral ST25 for 30 min, once a day for 14 consecutive days. The discharge time for the first black stool was recorded after gavage of mixed suspension fluid of active carbon (2 mL) for assessing the gastrointestinal motility. The colonic EMG was recorded by using a pair of silver electrodes and bioelectric amplifier. The expression of SP and VIP in the colonic tissue was detected by immunohistochemistry.
RESULTS
Following mode-ling, the colonic EMG amplitude, the discharge time for the first black stool and VIP immunoactivity were significantly increased (<0.01), and the EMG frequency and SP immunoactivity were significantly decreased (<0.01) in the model group compared with the control group. Compared with the model group, the increase of the discharge time for the first black stool, EMG amplitude and VIP immunoactivity, the decrease of EMG frequency and SP immunoactivity were reversed in the 3 EA groups (<0.01, <0.05). The therapeutic effect of 100 Hz-EA was notably weaker than that of both 2 Hz-EA and 2 Hz/100 Hz-EA in up-regulating EMG frequency and SP immunoactivity and in down-regulating the discharge time for the first black stool, EMG amplitude and VIP immunoactivity (<0.05, <0.01). There was no significant difference between the 2 Hz/100 Hz-EA and 2 Hz-EA groups (>0.05).
CONCLUSION
EA can accelerate colonic EMG activities, which may be associated with its functions in down-regulating VIP immunoactivity and up-regulating SP immunoactivity in the colonic tissues. The therapeutic effects of 2 Hz/100 Hz-EA and 2 Hz-EA are better than that of 100 Hz-EA.
Topics: Acupuncture Points; Animals; Colon; Constipation; Electroacupuncture; Electromyography; Male; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide
PubMed: 36036105
DOI: 10.13702/j.1000-0607.20210638