Targeting TRPV1 and TRPA1: A feasible strategy for natural herbal medicines to combat postoperative ileus.

Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.

Shenhuang plaster ameliorates the Inflammation of postoperative ileus through inhibiting PI3K/Akt/NF-κB pathway.

BACKGROUND: Although Shenhuang plaster (SHP) from traditional Chinese medicine prescriptions, has the potential to promote the recovery progression of postoperative ileus (POI), the underlying mechanism remains elusive. Along these lines, in this work, both in vivo and in vitro studies were conducted to systematically explore the regulatory effect and mechanism of SHP on the inflammatory response of the intestinal basal layer in the POI model mice. METHODS: Intestinal manipulation in mice was utilized for the POI model. The impact of SHP in response to POI was evaluated by carrying fluorescein-labeled dextran, histomorphology, immunohistochemistry, in combination with flow cytometry analysis and transcriptome RNA sequencing in vivo. Besides, the cytotoxicity of the SHP treatment on RAW264.7 cells was detected by cell counting kit-8 (CCK-8), the biological effects were assessed by polymerase chain reaction (PCR) and the potential influences on the PI3K/Akt/NF-κB pathway were identified through detecting the expression levels of P85, AKT, IKK and P65 by western blot in vitro. RESULTS: The implementation of the SHP treatment could significantly reduce the expressions of interleukin (IL)- 1ß and tumor necrosis factor (TNF)-α in the intestine, whereas the recovery of gastrointestinal motility is promoted. In addition, SHP can regulate the polarization of macrophages, indicating that the proportion of the M2 type is increased after the application of the SHP treatment. In addition, SHP inhibited the activity of PI3K/AKT/NF-κB signaling pathway-related proteins. CONCLUSION: SHP can significantly ameliorate the inflammatory response of POI and at the same time promote the recovery of gastrointestinal motility. Its mechanism may be mediated by the polarization of macrophages through the PI3K/AKT/NF-κB signaling pathway.

Hangekobokuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus through its anti-inflammatory action.

BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT. METHODS: HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed. RESULTS: HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.

Increased Risk of Meconium-Related Ileus in Extremely Premature Infants Exposed to Antenatal Magnesium Sulfate.

INTRODUCTION: We experienced an increased incidence of meconium-related ileus (MRI) in extremely premature infants (EPIs) while adopting the antenatal magnesium sulfate (MgSO4) protocol for fetal neuroprotection in our neonatal intensive care unit. This study aimed to test whether antenatal MgSO4 use was associated with increased risk of MRI in EPIs. METHODS: The incidences of complicated MRI requiring aggressive enema or surgical intervention and other intestinal complications were compared among period 1 (January 2012-December 2013, n = 79), before adoption of the antenatal MgSO4 protocol for fetal neuroprotection; period 2 (January 2014-March 2016, n = 72), when the protocol was adopted; and period 3 (April 2016-September 2018, n = 75), when the protocol was temporarily withdrawn due to concern regarding intestinal complications in EPIs. RESULTS: Despite similar baseline clinical characteristics among infants across the study periods, the MRI and MRI with surgical treatment incidences were higher in period 2 than those in periods 1 and 3 (13% vs. 8% and 6%, p = 0.391, and 11% vs. 0% and 1%, p = 0.001, respectively). In multivariable analysis, exposure to antenatal MgSO4 independently increased the risk of MRI (adjusted odds ratio, 3.8; 95% confidence interval, 1.4, 10.6). CONCLUSION: Antenatal MgSO4 may increase the risk of MRI, frequently requiring surgical intervention, in EPIs with a gestational age of 25 weeks or less.

Retrospective study on the use of lidocaine constant rate infusions for the treatment of ileus in ruminants and camelids.

Limited knowledge exists regarding the use of lidocaine as a prokinetic in ruminants and camelids to treat gastrointestinal ileus. In this retrospective study, ruminant and camelid cases diagnosed with ileus and treated with a lidocaine constant rate of infusion were assessed for adverse reactions and medical outcomes. A review of medical records was performed to identify cases in which lidocaine was administered as a prokinetic. Ten cases were identified consisting of 8 cattle, 1 goat, and 1 alpaca. Nine animals improved with a lidocaine treatment. No adverse effects were reported during lidocaine administration. Nine animals were discharged, and 1 was euthanized.

The effect of compound Da-Cheng-Qi Decoction on the treatment of malignant bowel obstruction with transnasal ileus tube.

OBJECTIVE: To study the effect of compound Da-Cheng-Qi Decoction (CDCQD) on the treatment of malignant bowel obstruction (MBO) with transnasal ileus tube (TIT). METHODS: We observed 30 cases of MBO from July 2018 to August 2019. The patients were divided into the control group (n = 15) and the CDCQD group (n = 15) according to a random number table. All patients were inserted the TIT after admission. Twenty-four hours later, the CDCQD group began to take 100 ml CDCQD twice a day for 7 days. The control group took the plain boiled water instead. Other treatment was the same in the two groups. The waistline reduction, the release time of abdominal pain and distention, recovery of exhaust and defecation time, drainage volume of TIT were observed and compared between the two groups. RESULTS: Three days after insertion of TIT, the abdominal plain film was re-examined in the two groups. Most of the patients' gas-liquid level disappeared and there was no significant difference between the two groups (P > 0.05). The effective rate of CDCQD group (86.7%) was significantly higher than that of control group (53.3%). The recovery time of exhaust and defecation in the CDCQD group was earlier than that in the control group (P < 0.05). The daily drainage volume of TIT in the CDCQD group was less than that in the control group, especially from the fourth day to the sixth day after insertion of TIT, with a significant difference (P < 0.05). CONCLUSION: TIT is an effective treatment for patients with MBO. With the basis of TIT treatment, CDCQD therapy can improve the curative effect of MBO. It can promote intestinal exhaust and defecation and improves the curative effect of palliative treatment of MBO. It is an effective method to assist Tit in the treatment for MBO patients.

Preventive effect of daikenchuto, a traditional Japanese herbal medicine, on onset of ileus after gynecological surgery for malignant tumors.

BACKGROUND: Postoperative ileus is a major complication of abdominal surgical procedures. The purpose of this study was to investigate preventive effect of daikenchuto (DKT) on onset of ileus in patients who received gynecological surgery for malignant tumors. METHODS: A total of 904 patients who received gynecological surgery for malignant tumors by opening retroperitoneum along with retroperitoneal lymph node dissection during a period between 2004 and 2018 were included in this retrospective study. The retroperitoneum was not sutured in all patients. Comparisons were made for proportion of patients developing ileus (frequency of postoperative ileus onset), timing of ileus onset, and treatment types for ileus among following three groups: a group treated with enema or laxatives to release gas if they did not pass the intestinal gas for 3 days postoperatively (Group A, n = 152); a group treated with adhesion-inhibitory absorptive barrier at the opening to the retroperitoneum (Group B, n = 188); and a group treated with adhesion-inhibitory absorptive barrier and oral intake of DKT 7.5 g per day (Group C, n = 564). RESULTS: The frequency of ileus onset significantly decreased in both Groups B (4.8%) and C (3.5%) compared to Group A (16.4%). Furthermore, the frequency of ileus onset was significantly less in Group C compared to Group B. For the treatment types, frequency of ileus, which was successfully treated only with conservative therapy, was the same for Groups B and C. However, incidence of serious ileus that required surgery decreased by 45% in Group C (2/564) compared to Groups A (2/152) and B (3/188). CONCLUSIONS: Results suggest that DKT prevents development of serious ileus after gynecological surgery for malignant tumors and therefore contributes to improvement in patients' QOL.

Effects of Cassia alata Linn on bowel function recovery following surgery for gynecological cancer: A randomized controlled trial.

BACKGROUND: Postoperative ileus is a common complication following abdominal surgery. This study was undertaken to determine the effectiveness and safety of Cassia alata Linn in stimulating gastrointestinal function recovery among women with gynecologic cancer who had undergone laparotomy for surgical staging or cytoreductive surgery. METHODS: A total of 90 participants were randomly allocated to postoperative consumption of either Cassia alata Linn tea (n = 45) or warm water (N = 45). Outcomes of interest included time to first passage of flatus, time to first defecation, time to toleration of solid food, and ileus symptoms. Differences between the groups were measured as mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). RESULTS: Women allocated to the Cassia alata Linn group had shorter times to first passage of flatus (MD -8.53; 95% CI -3.69, -13.38 h) and first defecation (MD -19.83; 95% CI -11.18, -28.48 h) compared with controls. There were no differences in terms of time to toleration of solid food (MD 0.26; 95% CI -2.13, 1.61 h) or ileus symptoms (OR 0.10; 95% CI 0.01, 1.94) between the two groups. CONCLUSION: Postoperative consumption of Cassia alata Linn hastens gastrointestinal function recovery after laparotomy in women with gynecologic cancer.

Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.

PURPOSE: Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). METHODS: A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. RESULTS: The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. CONCLUSIONS: The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. TRIAL REGISTRATION NUMBER: UMIN000026292.

The effect of somatostatin retained enema in the treatment of pancreatic ileus.

OBJECTIVE: To analyze the therapeutic effects of somatostatin retained enema in the treatment of pancreatic ileus in the clinic. PATIENTS AND METHODS: 79 patients randomly divided into 41 cases in the observation group and 38 cases in the control group were analyzed. The control group applied basic treatment plan. The observational group applied the same treatment combined with somatostatin retained enema, conducted twice every day and at least 30 minutes every time. Every 7 days' treatment made a course. The clinical therapeutic effects were compared. RESULTS: The levels of the hemo diastase and urinary amylase in both groups were decreased prominently after treatment. The levels of blood calcium were prominently increased (p<0.05) with even more improvement in the observation group (p<0.05). The relief times of the abdominal ache and distention, the recovery time of bowel sound and the first defecation time in the observation group were shorter (p<0.05) than those in the control group. The levels of blood serum IL-6 and TNF-α in the two groups were prominently decreased (p<0.05) after treatment, with even more obvious improvement in the observation group. The therapeutic effective rate of the observational group was prominently higher (p<0.05) than that in the control group. The occurrence rate of the complications was lower. CONCLUSIONS: The application of somatostatin retained enema in the treatment of pancreatic ileus is preferably safe and effective, and it deserves clinical promotion and application.

Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.

BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.

Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.

Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20 mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-α, IL-1ß, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with significance at doses of 10 and 20 mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis.

Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.

BACKGROUND/AIMS: Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. METHODOLOGY: Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. RESULTS: Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P < 0.05). There were no significant intergroup differences in secondary endpoints and adverse events. CONCLUSIONS: DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

Rikkunshito, a Kampo medicine, ameliorates post-operative ileus by anti-inflammatory action.

Rikkunshito (RKT), a Kampo (Japanese herbal) medicine, is used as a prokinetic for patients with various diseases including functional dyspepsia. RKT promotes delayed gastric emptying via 5-HT3 receptor blockade. Otherwise, RKT increases ghrelin release via 5-HT2B and 5-HT2C receptor activation. Recent studies revealed that ghrelin and 5-HT3 receptor antagonists have an anti-inflammatory effect. So we hypothesize that RKT may have an anti-inflammatory action in the post-operative ileus. Intestinal manipulation (IM) was applied to the distal ileum of mice. RKT was administered orally 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, and gastric emptying were analyzed. We also investigated the effects of the 5-HT3 receptor agonist m-chlorophenylbiguamide (mCPBG) and ghrelin-receptor antagonist [D-Lys3]-GHRP-6 on the ameliorative action of RKT. RKT treatment led to recovery of the delayed intestinal transit and gastric emptying rate induced by IM. RKT significantly inhibited the infiltration of neutrophils and macrophages. [D-Lys3]-GHRP-6 reduced and mCPBG partially reduced the RKT-mediated anti-inflammatory activity, as monitored by infiltrating macrophages and neutrophils. RKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency, in addition to prokinetic action. The RKT-induced anti-inflammatory activity may be partly mediated by inhibition of the 5-HT3 receptor and ghrelin release.

Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

BACKGROUND: Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action. METHOD: Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice. RESULTS: DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice. CONCLUSIONS: In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

Effects of dried Citrus unshiu peels on gastrointestinal motility in rodents.

Aqueous extracts of the dried mature (ANP-W) and immature Citrus unshiu peels (CUP-W) have been used as a traditional folk medicine for the treatment of gastrointestinal (GI) motility disorders in Korea. In the present study, neither ANP-W nor CUP-W exhibited significant toxicity even at an oral dose of 5 g/kg to mice. The effects of ANP-W and CUP-W on GI motor function were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal mice and rats with experimental GI motility dysfunctions (GMDs). In normal mice, the ITR was significantly increased by ANP-W (0.1-1 g/kg) in a dose dependent manner, whereas CUP-W elicited no significant change. GMD was induced by appropriate surgery or an intraperitoneal injection of acetic acid to the rats. The ITR in the GMD rats was significantly retarded compared to that in normal rats. However, the retardation was significantly inhibited by ANP-W (0.1-1 g/kg) in a dose dependent manner. The above results suggest that ANP-W has the potential for development as a prokinetic agent that may prevent or alleviate GMD in human patients.

Effect of jatrorrhizine on delayed gastrointestinal transit in rat postoperative ileus.

OBJECTIVES: Postoperative ileus is major cause of postoperative complication and prolonged hospitalization. Jatrorrhizine, which is a protoberberine alkaloid isolated from the medicinal plants Berberis aristata and Coptis chinensis, has been found to increase contractility of gastric antral and ileum smooth muscles of rat gastrointestinal tract. We have investigated whether jatrorrhizine could offset gastrointestinal transit in rat with postoperative ileus. METHODS: Postoperative ileus was induced by laparotomy with intestinal manipulation under anaesthesia. Gastrointestinal transit was evaluated by measurement of gastric emptying, geometric centre and the migration of Evans blue. KEY FINDINGS: Postoperative ileus significantly delayed gastric emptying and intestinal transit. Jatrorrhizine dose-dependently (0.1, 0.3 and 1 mg/kg) offset delayed gastric emptying and intestinal transit (geometric centre and the migration of Evans blue) in postoperative ileus. Pretreatment of animals with atropine inhibited the action of jatrorrhizine on gastric emptying and intestinal transit, but pretreatment of animals with SB204070 did not influence the effect of jatrorrhizine on gastric emptying and intestinal transit in postoperative ileus. CONCLUSIONS: Jatrorrhizine offset postoperative ileus-induced delayed gastric emptying and intestinal transit in rats, an action mediated via the cholinergic pathway, but not involving activation of 5-HT(4) receptors.

Gastric and small bowel ileus after severe burn in rats: the effect of cyclooxygenase-2 inhibitors.

Gastrointestinal (GI) ileus is a common complication after severe burns. Selective cyclooxygenase-2 inhibitors (COX-2i) improved post-operative ileus, but its effect on burn-induced GI dysmotility is unknown. Our aim was to test whether a COX-2i improves gastric emptying (GE) and small bowel transit (SBT) after burn. Experiment on GE: rats were anesthetized and randomized into sham/scald burn, treated/untreated with COX-2i. Six hours after burn, rats received a phenol red meal and were sacrificed 30 min later. Gastric emptying was determined based on the percentage of phenol red recovered in harvested stomachs. Experiment on SBT: rats received a duodenostomy and were scald/sham burned 5 days later. Six hours after burn, rats received a phenol red meal through the duodenostomy catheter and were sacrificed 100 min later. Geometric center (GC) was calculated for SBT. GE was decreased significantly in burned vs. sham animals (p<0.001). SBT was significantly impaired in burned vs. sham animals (p<0.001). The COX-2i improved GE in the burn rats but not GE in the control rats or SBT in the burn rats. COX-2i improves burn-induced delayed GE, suggesting the mediation of the latter via the prostaglandin pathway.

Hepatic derangement following N-Acetylcysteine enemas in an infant with cystic fibrosis.

We discuss an infant with MI secondary to cystic fibrosis, who was managed surgically by a double barrel ileostomy for mid - small bowel atresia and developed severe faecal impaction in the post - operative period. The faecal impaction was treated successfully with oral NAC and 0.2% NAC contrast enemas. The patient's liver function tests revealed a dramatic increase in transaminases and bilirubin contemporaneous with the administration of the enemas. The levels showed a spontaneous improvement after discontinuation. This is only the second reported case of hepatotoxicity secondary to NAC enemas in the literature. While our experience offers modest support for the use of NAC, its efficacy is not yet proven and paediatric surgeons using NAC in the enema form need to closely monitor liver function contemporaneous with this agent's administration and adjust their treatment accordingly.

The pharmacological effects of Daikenchuto, a traditional herbal medicine, on delayed gastrointestinal transit in rat postoperative ileus.

The effect of Daikenchuto, a traditional herbal medicine, on gastrointestinal hypoperistalsis in postoperative ileus (POI) was investigated. POI was induced by laparotomy with manipulation of the gastrointestine under anesthesia, and gastrointestinal transit was calculated by migration of Evans blue. Daikenchuto (270 - 2,700 mg/kg, p.o.) dose-dependently improved the delayed gastrointestinal transit in POI. This effect of Daikenchuto was partially inhibited by SB204070 (1 mg/kg, s.c.), a 5-hydroxytriptamine(4) (5-HT(4))-receptor antagonist and completely abolished by atropine (1 mg/kg, s.c.), a muscarine-receptor antagonist. Among the constituents of Daikenchuto, the medical herb zanthoxylum fruit (60 mg/kg, p.o.) and maltose syrup (2,400 mg/kg, p.o.) significantly ameliorated the delayed gastrointestinal transit, but ginseng and processed ginger did not affect the gastrointestinal transit in the rat POI. The improvement induced by zanthoxylum fruit was also inhibited by atropine or SB204070. In addition, the high osmotic pressure of the maltose syrup (2400 mg/10 mL per kg) was related to the improvement of delayed gastrointestinal transit. These results demonstrated that Daikenchuto ameliorates postoperative hypoperistalsis via cholinergic nerves and 5-HT(4) receptors and that osmotic pressure also may be involved in this action. Moreover, zanthoxylum fruit and maltose syrup were crucial medical herbs contributing to the ability of Daikenchuto.