Abstract. In this study, we attempted to clarify the mechanism of tachykinin-induced motor response in isolated smooth muscle preparations of the human colon. Fresh specimens of normal colon were obtained from patients suffering from colonic cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with circular direction was monitored isometrically. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) produced marked contraction. All of these contractions were inhibited by saredutant, a selective NK 2 -R antagonist, but not by CP122721, a selective NK 1 -R antagonist or talnetant, a selective NK 3 -R antagonist. βAla 8 -NKA(4-10) induced concentration-dependent contraction similar to NKA, but Sar 9 -Met 11 -SP and Met-Phe 7 -NKB did not cause marked contraction. Colonic contraction induced by βAla 8 -NKA(4-10) was completely blocked by saredutant, but not by atropine. Tetrodotoxin or N G -nitro-L-arginine methyl ester pretreatment significantly enhanced βAla 8 -NKA(4-10)-induced contraction. Immunohistochemical analysis showed that the NK 2 -R was expressed on the smooth muscle layers and myenteric plexus where it was also co-expressed with neuronal nitric oxide synthase in the myenteric plexus. These results suggest that the NK 2 -R is a major contributor to tachykinin-induced smooth muscle contraction in human colon and that the NK 2 -R-mediated response consists of an excitatory component via direct action on the smooth muscle and an inhibitory component possibly via nitric oxide neurons.

A previously healthy 35-year-old man visited the emergency room complaining of epigastric pain and vomiting. The pain was sudden in onset. His blood tests were within normal limits except for a mild neutrophilia of 14 300/μL. Enhanced abdominal CT scan showed the small intestine dilated into the space between the portal vein and inferior vena cava from the foramen of Winslow. Under the diagnosis of herniation through the foramen of Winslow (HFW), we performed emergency laparoscopic surgery. Laparoscopy revealed an internal herniation of the dilated small intestine through the foramen of Winslow. Because the herniated small intestine was viable, intestinal resection was unnecessary. We released the incarceration under laparoscopy. HFW is very rare and often overlooked, but abdominal CT examination enabled a precise preoperative diagnosis because of characteristic findings. We should consider the possibility of HFW in patients with internal herniation of unknown origin. Laparoscopic surgery for HFW is effective.

Abstract. TAK-480, 4-(difluoromethoxy)-N-((1R,2S)-2-(((3aR,4R,9bR)-4-(methoxymethyl)-2, 3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl)carbonyl)cyclohexyl)benzamide, is a novel tachykinin NK 2 -receptor antagonist. In this study, we investigated its antagonistic activity and efficacy in animal models of visceral hypersensitivity and stimulated bowel function which have been implicated to underlie the symptoms in irritable bowel syndrome (IBS). TAK-480 showed potent binding affinity for human NK 2 receptors with a marked species difference and a 10,000-fold selectivity versus NK 1 and NK 3 receptors. TAK-480 dose-dependently antagonized colonic contractions induced by administration of the NK 2 receptor-selective agonist beta-Ala 8 -NKA(4-10) (βA-NKA) in anesthetized rabbits. In a rabbit model of intracolonic zymosan-induced visceral hypersensitivity, TAK-480 markedly inhibited the visceromotor response to colorectal distension, in contrast to the moderate inhibition by the serotonin 5-HT 3 -receptor antagonist alosetron. In addition, TAK-480 suppressed ricinoleic acid-induced defecation without affecting spontaneous defecation in guinea pigs, whereas alosetron suppressed both. Furthermore, TAK-480 inhibited smooth muscle contractions produced by natural tachykinins (substance P, neurokinin A, and neurokinin B) as well as βA-NKA in an isolated human colon. In conclusion, the novel NK 2 -receptor antagonist TAK-480 improved visceral hypersensitivity and accelerated defecation without causing constipation in experimental animals. Furthermore, the potent functional blockade of NK 2 receptors in human colon might suggest the potential effectiveness of TAK-480 in IBS patients.

The current study presents a mesenteric mesenchymal tumor case, with unusual features in diagnostic imaging and histology. A 16-year-old male was admitted to the hospital with abdominal pain. Computed tomography (CT) revealed an abdominal mass, 2 cm in diameter. The results of contrast-enhanced CT, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography indicated no specific features suggestive of its histology. Two arteries branching from the superior mesenteric artery were observed feeding the hypervascular tumor. After endoscopic and other laboratory findings revealed no additional lesions, the lesion was diagnosed as a primary mesenteric tumor. As the possibility of malignancy and future bleeding from this tumor could not be ruled out, a resection of the tumor was performed. During the surgery, the tumor, which was well circumscribed and hypervascular, was located in the mesentery of the jejunum. The resected tumor did not exhibit typical histological characteristics, and was labeled as ‘myxoid smooth muscle neoplasm of uncertain biologic potential’. At 2 years after surgery, the patient remained well without evidence of recurrence. As primary mesenteric tumors are rare, particularly in young patients, it is considered important that this type of unusual tumor be included in the differential diagnosis for mesenteric tumors.

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