Increased Bile Acid Signals After Duodenal-Jejunal Bypass Improve Non-alcoholic Steatohepatitis (NASH) in a Rodent Model of Diet-Induced NASH.

BACKGROUND: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects. We sought to investigate the effects and mechanisms of bariatric surgery on NASH improvement. METHODS: Male Sprague-Dawley rats were fed by a high-fat and high-fructose diet, which results in obesity, insulin resistance, and NASH. Rats underwent duodenal-jejunal bypass (DJB), which is a main component of bariatric procedures. The liver pathological findings and the expression level of mRNA of FXR were investigated. The plasma BA level was measured in peripheral and portal vein blood. RESULTS: DJB suppressed weight gain, improved insulin resistance, and ameliorated NASH mainly in a point of inflammation. The plasma BA level along with the expression of FXR and its target transcriptional factor, small heterodimer partner (SHP), in the liver were elevated. CONCLUSIONS: DJB has a direct effect on NASH improvement, and there is a possibility that an anti-inflammatory effect is functioning as a part of the mechanism. The increase of plasma bile acid level followed by the stimulation of FXR signaling may contribute to this phenomenon.

Biliopancreatic limb plays an important role in metabolic improvement after duodenal-jejunal bypass in a rat model of diabetes.

BACKGROUND AND AIMS: Roux-en-Y gastric bypass improves glucose metabolism in clinical practice, and duodenal-jejunal bypass (DJB), an experimental bypass procedure, also improves metabolism in animals. However, the mechanism remains controversial; especially, the role of the biliopancreatic limb (BP-limb) remains unclear. Our aim was to examine the importance of the function of the BP-limb after DJB using a novel operative model. METHODS: Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into the following groups: DJB with a short alimentary limb (A-limb) and long BP-limb (B-DJB group), DJB with jejunectomy (J-DJB group) in which the entire length of the jejunum used for the BP-limb of the B-DJB group was excised; and a sham operation group. Glucose tolerance, plasma bile acid levels, and the gut microbiota were assessed postoperatively. RESULTS: Glucose tolerance was improved and weight gain was suppressed after surgery in the B-DJB group. In contrast, these effects were cancelled in the J-DJB group. The plasma levels of bile acids in the B-DJB group were greater than those in other groups. The analysis of gut microbiota showed distinct differences between the B-DJB and other groups; especially, the relative abundance of genus Bifidobacterium was much higher in the B-DJB group. CONCLUSION: The BP-limb played an important role in the control of weight gain, glucose tolerance, and increased plasma bile acid levels after DJB in this rat model of type 2 diabetes mellitus. Plasma bile acids and gut microbiota may be involved in these processes.

Intracolonic Administration of the TRPA1 Agonist Allyl Isothiocyanate Stimulates Colonic Motility and Defecation in Conscious Dogs.

BACKGROUND: The aim of the present study was to investigate the effects of the intracolonic transient receptor potential (TRP) A1 agonist allyl isothiocyanate (AITC) on colonic motility and defecation. METHODS: The effects of AITC administered into the proximal colonic lumen on colonic motility and defecation were studied in neurally intact dogs equipped with strain-gauge force transducers on the colon, with or without various antagonists. Effects of intracolonic AITC were also studied in dogs with either transection/re-anastomosis (T/R) between the proximal and middle colon and complete extrinsic denervation of an ileocolonic segment. RESULTS: AITC increased colonic motility and induced giant migrating contractions (GMCs) with defecations in 75% of experiments in neurally intact dogs. These effects were inhibited by atropine, hexamethonium, ondansetron, and HC-030031 but unaltered by capsazepine. In dogs with T/R, the increase in colonic motility was inhibited in the middle-distal colon. In dogs with extrinsic denervation, the increase in colonic motility in the distal colon was decreased. CONCLUSIONS: Intracolonic AITC stimulates colonic motility and defecation via cholinergic, serotonergic, and TRPA1 pathways. Continuity of colonic enteric neurons plays an essential role in the intracolonic AITC-induced colonic motor response, while extrinsic nerves are important in occurrence and propagation of GMCs.

Role of the intraluminal contents and the continuity of intrinsic neurons in intracolonic capsaicin-induced contraction and defecation in dogs.

PURPOSE: We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation. METHODS: Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models. RESULTS: In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p < 0.05 compared to intact dogs). The effect of yohimbine (2 mg/kg) in inducing colonic contractions was unaltered after colonic cleansing and T/R; in contrast, yohimbine-induced defecation was not observed after colonic cleansing, but was unchanged after T/R. CONCLUSIONS: The continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

[Two cases of advanced gastric cancer achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose CDDP].

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.

[A case of Peutz-Jeghers syndrome with repeated small intestinal intussusception successfully treated by intraoperative endoscopic polypectomy].

Intestinal polyps are a distinctive feature of Peutz-Jeghers syndrome (PJS). These hamartomas can lead to significant complications such as intussusception or gastrointestinal bleeding which necessitate multiple laparotomies and bowel resections. In an operation for intestinal intussusception, it is preferable to simultaneously resect as many polyps as possible to prevent recurrence of complications caused by intestinal polyps. We report a case of a woman in her twenties with PJS, diagnosed as small intestinal intussusception caused by an intestinal polyp. We performed not only repair of the intussusception but also endoscopic polypectomy without resection of the small intestine. We successfully resected all polyps larger than 10mm from the duodenum to the ascending colon during the operation.

Perioperative oral administration of cystine and theanine enhances recovery after distal gastrectomy: a prospective randomized trial.

BACKGROUND: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. METHODS: Forty-three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single-blind, parallel-group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre- and postoperative interleukin (IL)-6, C-reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. RESULTS: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL-6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre- and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). CONCLUSIONS: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.

Enhancement of postoperative recovery by preoperative oral co-administration of the amino acids, cystine and theanine, in a mouse surgical model.

BACKGROUND & AIMS: Glutathione (GSH) is important in the control of immune responses, and its levels decline following trauma. We previously reported that the oral administration of cystine/theanine (CT) increased GSH synthesis and that CT intake inhibited intense exercise-induced inflammation. Based on these results, we hypothesised that CT inhibits surgically induced inflammation and promotes postoperative recovery. Our aim was to confirm this hypothesis using a mouse surgical model. METHODS: CT or a vehicle (V) was administered orally to mice once a day for 5 days, until the day of surgery. On the day of surgery, a sham operation or an intestinal manipulation was performed 2 h after the oral administration of CT or V. Levels of IL-6 in the blood and GSH in the intestine were analysed 2 h after surgery. Behavioural analysis was also undertaken after surgery. RESULTS: Treatment with CT inhibited the manipulation-induced increase in IL-6 in the blood and decrease in GSH in the intestine. There was a significant negative correlation between IL-6 in the blood and GSH in the intestine. In addition, behavioural analysis revealed that CT administration improved locomotor activity and food intake after surgery. CONCLUSION: These results suggest that CT suppresses inflammatory responses by inhibiting the surgically induced decrease in GSH in the small intestine and promotes postoperative recovery.