2-(Halogenated Phenyl) acetamides and propanamides as potent TRPV1 antagonists.

A series consisting of 117 2-(halogenated phenyl) acetamide and propanamide analogs were investigated as TRPV1 antagonists. The structure-activity analysis targeting their three pharmacophoric regions indicated that halogenated phenyl A-region analogs exhibited a broad functional profile ranging from agonism to antagonism. Among the compounds, antagonists 28 and 92 exhibited potent antagonism toward capsaicin for hTRPV1 with Ki[CAP] = 2.6 and 6.9 nM, respectively. Further, antagonist 92 displayed promising analgesic activity in vivo in both phases of the formalin mouse pain model. A molecular modeling study of 92 indicated that the two fluoro groups in the A-region made hydrophobic interactions with the receptor.

Discovery of 1-(1H-indazol-4-yl)-3-((1-phenyl-1H-pyrazol-5-yl)methyl) ureas as potent and thermoneutral TRPV1 antagonists.

A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Among them, the antagonists 26, 50 and 51 displayed highly potent antagonism with Ki(CAP) = 0.4-0.5 nM. Further, in vivo studies in mice indicated that these derivatives both antagonized capsaicin induced hypothermia, consistent with their in vitro activity, and themselves did not induce hyperthermia. In the formalin model, 51 showed anti-nociceptive activity in a dose-dependent manner.

A Korean experience of the use of Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research.

BACKGROUND/AIMS: Few bowel preparation scales have been validated. The Boston Bowel Preparation Scale (BBPS) is a novel bowel preparation scale in western countries. We validated the BBPS in Korean patients and assessed the relationship between the colon polyp detection rate and BBPS score. PATIENTS AND METHODS: This study was a prospective, single-center trial. The BBPS is a 10-point scale that assesses bowel preparation after the completion of all cleansing maneuvers. We assessed three segment scores (the right side, transverse section, and left side) and total BBPS scores during screening colonoscopy. In addition, we compared the BBPS scores with clinically meaningful outcomes such as the polyp detection rate and colonoscope withdrawal times. RESULTS: We enrolled 482 screening colonoscopies between January 2011 and January 2012. The mean (± standard deviation [SD]) BBPS score was 8.1 ± 1.1. Higher BBPS scores (≥8 vs <8) were associated with a higher polyp detection rate (44.9% vs. 33.0%, P = 0.042). The BBPS scores were inversely correlated with colonoscope withdrawal times (r = -0.167, P < 0.001). CONCLUSIONS: The BBPS is a valid and reliable measure for assessing bowel preparation during colonoscopy in Korean patients. The polyp detection rate is higher in patients with higher BBPS scores than in those with lower BBPS scores during a colonoscopic procedure.

[A prospective study of factors influencing on the clinical characteristics of colonic diverticulosis].

BACKGROUND/AIMS: The prevalence of colonic diverticulosis in Korea is increasing in conjunction with the adoption of western dietary pattern, extension of lifespan, and advances in diagnostic modalities. The clinical characteristics of colonic diverticulosis seem to be gradually becoming similar to those of Western societies. Therefore, factors associated with the clinical characteristics of colonic diverticulosis in Korea were investigated. METHODS: The data of 200 patients diagnosed with colonic diverticulosis using colonoscopy between May 2010 and April 2012 at Inje University Seoul Paik Hospital (Seoul, Korea) were prospectively collected. Clinical parameters acquired through a questionnaire include age, body mass index, waist circumference, exercise, diet, smoking, drinking habits, etc. Correlation between these factors and the clinical features of diverticulosis were analyzed. RESULTS: Mean age of the patients was 54.9±11.9 (range 17-79) years and male to female ratio was 2.2:1. Most diverticula were located on the right side of the colon (83%) and the mean number of diverticulum was 4.07±3.9. Factor associated with the location of diverticulum on the left side was age (p=0.001). There was a positive correlation between the waist circumference and the number of diverticulum (partial correlation coefficient r'=0.143, p=0.047). Diverticulitis occurred more frequently in younger patients than in older patients (p=0.002). CONCLUSIONS: Colonic diverticulosis in older patients is found more frequently on the left colon, and the number of diverticulosis is associated with central obesity.

Prognostic significance of Ki-67 expression in rectal carcinoid tumors.

BACKGROUND/AIMS: Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors. METHODS: We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis. RESULTS: The mean age (±SD) of the patients was 56.3±10.7 years, and the male : female ratio was 3.6 : 1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed. CONCLUSIONS: In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.

Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain.

The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

[A case of conservatively resolved intramural esophageal dissection combined with pneumomediastinum].

Intramural esophageal dissection (IED) is a rare form of esophageal injury. We report a rare case of spontaneous IED complicated with pneumomediastinum and successfully improved by conservative management. A 46-year-old man presented to the emergency department with chest pain and hematemesis. The endoscopic diagnosis was suspicious of IED. Chest CT scan performed to rule out complication noted IED combined with pneumomediastinum. He was managed conservatively with nil per oral, intravenous antibiotics and parenteral nutrition. Follow up study after 2 weeks later showed near complete resolution of IED. IED should be included in the differential diagnosis for unexplained acute chest pain, especially, associated with dysphagia and hematemesis. IED with pneumomediastinum or mediastinitis require prompt surgery. So far, there is no case report of IED combined with pneumomediastinum which resolved without surgical treatment. In this case, IED combined with pneumomediastinum has improved by conservative management, so we present a case report.

A case of cryptogenic multifocal ulcerous stenosing enteritis: differential diagnosis from Crohn's disease.

Cryptogenic multifocal ulcerous stenosing enteritis is a rare idiopathic disease of the small bowel. Its origin and pathophysiology have not been established. Clinicopathologic features include unexplained small bowel strictures with superficial ulceration, chronic or relapsing occlusion episodes. A 44-year-old man complained of recurrent colicky abdominal pain and dizziness. Laboratory tests indicated iron-deficiency anemia. There was no evidence of bleeding on esophagogastroduodenoscopic and colonofiberscopic examination. With capsule endoscopy, multiple mucosal ulcers were visualized in the jejunoileal area. A small-bowel series revealed severe strictures and the capsule was retained in the stenotic focus without obstructive symptoms. Small bowel segmental resection with end-to-end anastomosis was performed, and the histologic examination indicated cryptogenic multifocal ulcerous stenosing enteritis. After surgery, the patient's symptoms were completely resolved and his anemia was corrected. Cryptogenic multifocal ulcerous stenosing enteritis should be considered in cases of chronic or recurrent occlusion events and multiple small intestinal ulcers and strictures of unknown origin.