-
Current Treatment Options in... Dec 2016Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic... (Review)
Review
Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic assessments (including upper endoscopy) and measures of upper gut function (e.g., gastric emptying testing). Nausea and vomiting in this condition are postulated to result from aberrant peripheral or central neurohumoral activity. A substantial subset of patients satisfies this diagnosis as more than half of individuals referred for scintigraphic testing exhibit normal gastric emptying rates. No randomized, placebo-controlled trials of any medication treatment have been performed in CUNV. However, agents with potential therapeutic benefits in CUNV include antiemetic drugs, neuromodulatory treatments which are proposed to act by reducing gastric sensitivity, and medications with prokinetic action to stimulate upper gut propulsion. Recently approved drugs with antiemetic capability include serotonin antagonists with novel modes of delivery and neurokinin antagonists with or without additional serotonergic blocking capabilities. Existing neuroleptics and pain-modifying neuromodulatory therapies with fortuitous antiemetic benefits are being considered for their benefits in this disorder. Furthermore, current investigations will define potential therapeutic actions of agents that stimulate gastric emptying via action on gastroduodenal serotonin, motilin, and ghrelin receptors. This current research may broaden the treatment options for refractory cases of unexplained nausea and vomiting.
PubMed: 27726068
DOI: 10.1007/s11938-016-0110-2 -
Journal of Smooth Muscle Research =... 2013Migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal (GI) contractions in the interdigestive state. The physiological importance of... (Review)
Review
Migrating motor complex (MMC) is well characterized by the appearance of gastrointestinal (GI) contractions in the interdigestive state. The physiological importance of gastric MMC is a mechanical and chemical cleansing of the empty stomach in preparation for the next meal. MMC cycle is mediated via the interaction between motilin and 5-hydroxytryptamine (5-HT) by the positive feedback mechanism in conscious dogs. Luminal administration of 5-HT initiates duodenal phase II and phase III with a concomitant increase of plasma motilin release. Duodenal 5-HT concentration is increased during gastric phase II and phase III. Intravenous infusion of motilin increases luminal 5-HT content and induces phase III. 5-HT4 antagonists significantly inhibit both of gastric and intestinal phase III, while 5-HT3 antagonists inhibit only gastric phase III. These suggest that gastric MMC is regulated via vagus, 5-HT3/4 receptors and motilin, while intestinal MMC is regulated via intrinsic primary afferent neurons (IPAN) and 5-HT4 receptors. We propose the possibility that maximally released motilin by a positive feedback depletes 5-HT granules in the duodenal EC cells, resulting in no more contractions. Stress is highly associated with the pathogenesis of functional dyspepsia (FD). Acoustic stress attenuates gastric phase III without affecting intestinal phase III in conscious dogs, via reduced vagal activity. Subset of FD patients shows reduced vagal activity and impaired gastric phase III. The impaired gastric MMC may aggravate dyspeptic symptoms following a food ingestion. Maintaining MMC cycle in the interdigestive state is an important factor to prevent the postprandial dyspeptic symptoms.
Topics: Animals; Digestion; Dogs; Duodenum; Dyspepsia; Feedback, Physiological; Gastric Emptying; Humans; Intestines; Motilin; Myoelectric Complex, Migrating; Neurons, Afferent; Postprandial Period; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Stomach; Vagus Nerve
PubMed: 24662475
DOI: 10.1540/jsmr.49.99 -
Life (Basel, Switzerland) Aug 2021Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut... (Review)
Review
Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (1) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, based on a literature search of three scientific databases, and (2) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression based on allele frequency data after correction for potential confounders. It was observed that (1) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (2) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required and that these molecular pathways represent potential future mechanisms for antidepressant drug development.
PubMed: 34575041
DOI: 10.3390/life11090892 -
Clinical Gastroenterology and... Aug 2016This review of the pathophysiologic basis for gastroparesis and recent advances in the treatment of patients with gastroparesis shows that there are several novel... (Review)
Review
This review of the pathophysiologic basis for gastroparesis and recent advances in the treatment of patients with gastroparesis shows that there are several novel approaches to advance treatment of gastroparesis including diet, novel prokinetics, interventions on the pylorus, and novel forms of gastric electrical stimulation. The field of gastroparesis is likely to advance with further studies, with help from a guidance document from the Food and Drug Administration on gastroparesis, and with recent approval of the stable isotope gastric emptying test to ensure eligibility of participants in multicenter trials. Clinical experience and a formal, randomized, controlled trial provide insights on optimizing dietary interventions in patients with gastroparesis. This review addresses the biologic rationale of these different treatments, based on known physiology and pathophysiology of gastric emptying. The novel medications include the motilin agonist, camicinal; 5-HT4 receptor agonists, such as velusetrag; and the ghrelin agonist, relamorelin. New approaches target pylorospasm by stent placement, endoscopic pyloric myotomy, or laparoscopic pyloroplasty. These approaches offer the opportunity to achieve more permanent reduction of resistance to flow at the pylorus over the intrapyloric injection of botulinum toxin, which typically has to be repeated every few months if it is efficacious. A novel device, deployed in porcine stomach, involved per-endoscopic electrical stimulation. These promising approaches require formal, randomized, controlled trials and deployment in patients. The presence of concomitant antral hypomotility may be a significant factor in the responsiveness to interventions at the pylorus.
Topics: Diet Therapy; Electric Stimulation; Gastrointestinal Agents; Gastroparesis; Humans; Surgical Procedures, Operative
PubMed: 26762845
DOI: 10.1016/j.cgh.2015.12.033 -
Gut Mar 1992The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its... (Review)
Review
The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity. This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders. Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man. These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents.
Topics: Animals; Digestive System; Dogs; Erythromycin; Gastrointestinal Motility; Guinea Pigs; Humans; Motilin; Rabbits; Rats; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 1568663
DOI: 10.1136/gut.33.3.397 -
Iranian Journal of Public Health Nov 2021The aim of the present study was to systematically review the efficacy and safety of mecobalamin combined with prokinetic agents in diabetic gastroparesis (DGP). (Review)
Review
BACKGROUND
The aim of the present study was to systematically review the efficacy and safety of mecobalamin combined with prokinetic agents in diabetic gastroparesis (DGP).
METHODS
A variety of databases were searched from inception to Nov 2, 2018. RCTs of mecobalamin combined with prokinetic agents group (experimental group) versus prokinetic agents only group (control group) in DGP were included. RevMan 5.3 and Stata 12.0 were used to perform the meta-analysis. Finally, 24 RCTs with 1,878 patients were included.
RESULTS
The total efficacy rate was significantly higher in the experimental group (mecobalamin combined with prokinetic drugs) compared with the control group (prokinetic drugs alone) (<0.001), and the improvement was observed regardless of the administration route. Furthermore, the treatment group exhibited a significantly improved gastric emption rate (<0.001), motilin (<0.001) and recurrence rate (<0.001), and there was no statistical difference in the incidence of adverse reactions between two groups (=0.49).
CONCLUSION
Mecobalamin combined with prokinetic agents can significantly improve total efficacy rate and gastric emptying rate, decrease serum motilin and the recurrence rate without increasing adverse reactions in DGP. Thus, mecobalamin may can be used as a new therapeutic option for DGP.
PubMed: 35223590
DOI: 10.18502/ijph.v50i11.7570 -
Journal of Ethnopharmacology Sep 2023Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since... (Meta-Analysis)
Meta-Analysis Review
ETHNOPHARMACOLOGICAL RELEVANCE
Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient.
AIM OF THE STUDY
This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD.
METHODS
Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE [risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001]. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone [mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001]. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI.
CONCLUSIONS
These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.
Topics: Humans; Dyspepsia; Motilin; Drugs, Chinese Herbal; Phytotherapy; Plants, Medicinal; Medicine, Traditional
PubMed: 37127143
DOI: 10.1016/j.jep.2023.116518 -
World Journal of Gastroenterology Sep 2023Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA)... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available.
AIM
To explore the effect and mechanism of HPA inhibition in S-AGI patients.
METHODS
In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1, 3 and 7 d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI.
RESULTS
Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group ( < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased ( < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased ( < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups ( > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.
CONCLUSION
HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.
Topics: Humans; Gastrins; Interleukin-6; Motilin; Tumor Necrosis Factor-alpha; Sepsis; Lactic Acid; Abdominal Injuries; Fatty Acid-Binding Proteins; Heparin, Low-Molecular-Weight
PubMed: 37744293
DOI: 10.3748/wjg.v29.i35.5154 -
European Review For Medical and... Sep 2018To observe the effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing a total... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To observe the effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing a total hysterectomy.
PATIENTS AND METHODS
80 patients who underwent hysterectomy from April 2015 to June 2016 were randomly divided into two groups, with 40 patients in each group. The two groups received an intravenous infusion of hydromorphone or morphine for analgesia. The VAS pain score and Ramsey sedation score were recorded 4, 8, 12, 24, and 48 hours after the first dose of analgesia. The scores of nausea and vomiting were recorded. The levels of motilin were determined by radioimmunoassay before anesthesia, after anesthesia, during hysterectomy and 1 day after the operation. The results showed that the analgesic effect of hydromorphone was more rapid than morphine.
RESULTS
There were significant differences in VAS scores between the two groups at each time point (p<0.05), indicating that the analgesic effect of hydromorphone was better than morphine's one. The scores of Ramsay sedation were less than 6 points at each time point within 48 hours after the operation. The content of plasma motilin in the hydromorphone group was higher than that in the morphine group during the first day after anesthesia. There were 34 cases (85%) of mild nausea and vomiting within 24 hours after the operation in the hydromorphone group. In the morphine group, there were 16 cases (40%) of mild nausea and vomiting within 24 hours after the operation, 10 cases (25%) of severe nausea and vomiting.
CONCLUSIONS
The occurrence of severe malignant vomiting after the use of morphine was more than that after the use of hydromorphone. Normal level and function of motilin is the basis of avoiding nausea and vomiting. Too fast or too slow gastrointestinal motility can induce postoperative nausea and vomiting.
Topics: Adult; Aged; Analgesics, Opioid; Biomarkers; China; Double-Blind Method; Female; Humans; Hydromorphone; Hysterectomy; Infusions, Intravenous; Middle Aged; Morphine; Motilin; Pain, Postoperative; Postoperative Nausea and Vomiting; Risk Factors; Time Factors; Treatment Outcome
PubMed: 30229847
DOI: 10.26355/eurrev_201809_15837 -
Frontiers in Neuroscience 2016Feeding is an essential behavior for animals to sustain their lives. Over the past several decades, many neuropeptides that regulate feeding behavior have been... (Review)
Review
Feeding is an essential behavior for animals to sustain their lives. Over the past several decades, many neuropeptides that regulate feeding behavior have been identified in vertebrates. These neuropeptides are called "feeding regulatory neuropeptides." There have been numerous studies on the role of feeding regulatory neuropeptides in vertebrates including birds. Some feeding regulatory neuropeptides show different effects on feeding behavior between birds and other vertebrates, particularly mammals. The difference is marked with orexigenic neuropeptides. For example, melanin-concentrating hormone, orexin, and motilin, which are regarded as orexigenic neuropeptides in mammals, have no effect on feeding behavior in birds. Furthermore, ghrelin and growth hormone-releasing hormone, which are also known as orexigenic neuropeptides in mammals, suppress feeding behavior in birds. Thus, it is likely that the feeding regulatory mechanism has changed during the evolution of vertebrates. This review summarizes the recent knowledge of peptidergic feeding regulatory factors in birds and discusses the difference in their action between birds and other vertebrates.
PubMed: 27853416
DOI: 10.3389/fnins.2016.00485