A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system. Am J Physiol Gastrointest Liver Physiol 294: G1084-G1093, 2008. First published February 28, 2008 doi:10.1152/ajpgi.00345.2007.-Moderate rectal distension elicits recto-rectal reflex contractions and simultaneous rectointernal anal sphincter reflex relaxations that together comprise the defecation reflex. Both reflexes are controlled by 1) pelvic nerves, 2) lumbar colonic nerves, and 3) enteric nervous system. The aim of the present study was to explore a novel approach to repairing the defecation reflex dysfunction by using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from the anal verge was transected without damage to extrinsic nerves, and subsequent endto-end one-layer anastomosis was performed. Recovery of the defecation reflex and associated reflex pathways were evaluated. Eight weeks after sectioning of intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to the control level, accompanied with regeneration of reflex pathways. The 5-HT 4-receptor agonist mosapride (0.5 and 1.0 mg/kg) significantly (P Ͻ 0.01) enhanced the recovered defecation reflex 8 wk after surgery. Two weeks after local treatment with brain-derived neurotrophic factor (BDNF: 10 Ϫ6 g/ml) at the rectal anastomotic site, the recto-internal anal sphincter reflex relaxations recovered and some bundles of fine nerve fibers were shown to interconnect the oral and anal ends of the myenteric plexus. These results suggested a possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system with local application of BDNF.brain-derived neurotrophic factor; internal anal sphincter THE DEFECATION REFLEX, which can be elicited by moderate rectal distension, involves simultaneous recto-rectal contractions (R-R reflex) and recto-internal anal sphincter reflex relaxation (R-IAS reflex). These coordinated responses involve both extrinsic reflexes via autonomic nervous system and intrinsic reflexes via enteric nervous system (17, 19 -21, 26). The plasticity of these intrinsic reflex pathways has been shown in models involving chronic destruction of lumbar and sacral cords in guinea pig (9, 10). After the lower anterior resection for rectal cancer, however, long-lasting defecation disturbances occur in many patients owing to the impairment of reflex pathways.Recently, we have reported that the 5-HT 4 receptor agonist mosapride enhances the intrinsic R-R and R-IAS reflexes in the spinal cord injury model as well as in intact guinea pigs. This indicates that 5-HT 4 -receptor activation can enhance intrinsic R-R and R-IAS reflexes that are functionally compromised after deprivation of extrinsic nerves and that this action is mediated through intrinsic pathways (9, 10). Accordingly, following lower anterior resection, mosapride can enhance the refl...
Distension-evoked reflex of rectorectal (R-R) contractions and rectointernal anal sphincter (R-IAS) relaxations can be generated in guinea pigs through an extrinsic sacral excitatory neural pathway (pelvic nerves) as well as intrinsic cholinergic excitatory and nitrergic inhibitory pathways. The aim of the present study was to create intrinsic R-R and R-IAS reflex models by pithing (destruction of the lumbar and sacral cords; PITH) and to evaluate whether the prokinetic benzamide mosapride, a 5-HT(4) receptor agonist, enhances these reflexes. The mechanical activities of the R-R and R-IAS were recorded in the anesthetized guinea pig on days 2-9 after PITH. Although the basal rectal pressure at distension after PITH was significantly lower than control, the reflex indexes of R-R contractions and synchronous R-IAS relaxations were unchanged between days 4 and 9 after PITH. The frequency of spontaneous rectal and IAS motility were also unchanged. Immunohistochemical studies revealed that the distribution of myenteric and intramuscular interstitial cells of Cajal (ICC) were not altered after PITH. Mosapride (0.1-1.0 mg/kg iv) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indexes (maximum: 2.76) from control (1.0) 6-9 days after PITH. The 5-HT(4) receptor antagonist, GR-113808 (1.0 mg/kg iv) decreased the R-R and R-IAS reflex indexes by approximately 50% and antagonized the effect of mosapride (1.0 mg/kg iv). The present results indicate that mosapride moderately enhanced intrinsic R-R and R-IAS reflexes functionally compensated after deprivation of extrinsic nerves, mediated through endogenously active intrinsic 5-HT(4) receptors.
The rectal distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations in guinea pigs were generated through the extrinsic sacral excitatory nerve pathway (pelvic nerves) and the intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The aim of the present study was to evaluate whether a prokinetic benzamide, mosapride, enhances the R-R and R-IAS reflexes mediated via 5-HT4 receptors in the guinea pig. The mechanical activities of the R and IAS were recorded with a balloon connected to a pressure transducer and a strain gauge force transducer in the anesthetized guinea pig with intact spinal-intestinal pathways. Gradual and sustained rectal distension evoked R-R contractions and synchronous R-IAS relaxations. Mosapride (0.1-1.0 mg/kg i.v.) dose-dependently enhanced both R-R and R-IAS reflex responses. Reflex indexes for R-R and R-IAS maximally increased from 1.0 (control) to 1.92 and 1.88, respectively. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg i.v.), antagonized the enhancement of the R-R and R-IAS reflexes induced by mosapride 1.0 mg/kg i.v. The present results indicate that mosapride enhanced the R-R and R-IAS reflexes mediated through 5-HT4 receptors.
As far as the authors are aware there has been no report of the EGFR mutation of MM in Japanese cases, but in this study EGFR missense mutations were detected in some cases. EGFR mutation results were not related to immunohistochemical and FISH analysis.
A novel glucose (Glc)-responsive gel formed by worm-like micelles (WLMs) has the potential to provide a self-regulating insulin delivery system. We have prepared a WLM gel system using 75 mM cetyltrimethylammonium bromide, 75 mM phenylboronic acid, and water. At pH 9.4, this gel-like system was highly viscous and supported its own weight, and dynamic viscoelasticity measurement indicated that it contained long and entangled WLMs. The visual observation of gels prepared to include >6 mM Glc revealed that these adopted a sol-like appearance, whereas those prepared to include a control compound (2-10 mM diethylene glycol) retained their gel-like appearance. The storage modulus ( G') of this system decreased as the Glc concentration increased (2-10 mM), indicating a gradual shortening of the WLMs. In vitro release was evaluated using a test compound (fluorescein isothiocyanate dextran) in a microsized flow system. By 120 min, the release of this compound from the WLM gel was around 27-fold greater in the presence of 100 mM Glc than without Glc or with 100 mM diethylene glycol. This demonstrated the successful preparation of a WLM gel that showed an altered drug release rate, depending on Glc concentration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.