Hybrid pharmacophore design and synthesis of donepezil-inspired aurone derivative salts as multifunctional acetylcholinesterase inhibitors.

Flavonoids, a ubiquitous group of plant polyphenols, are well-known for their beneficial effects on human health. Their phenylchromane skeletons have structural similarities to donepezil [the US FDA-approved drug used to treat Alzheimer's disease (AD)]. The objective of this study was to design and synthesize valuable agents derived from flavonoids for relieving the symptoms of AD. A variety of flavonoid derivative salts incorporating benzylpyridinium units were synthesized and several of them remarkedly inhibited acetylcholinesterase (AChE) activity in vitro. Additionally, aurone derivative salts protected against cell death resulting from t-BHP exposure in rat pheochromocytoma PC12 cells and slightly promoted neurite outgrowth. Furthermore, they potently suppressed the aggregation of amyloid-ß (Aß1-42). Our findings highlight the effectiveness of donepezil-inspired aurone derivative salts as multipotent candidates for AD.

[A case of colon cancer with multiple liver metastases responding ot S-1 as third-line treatment following FOLFIRI and FOLFOX].

A 73-year-old man had undergone right hemicolectomy for advanced colon cancer in May 2006, and he concurrently had multiple liver metastases. After the operation, the patient was given chemotherapy with FOLFIRI. A partial response was achieved for twelve months, and then the liver tumors enlarged. Second-line chemotherapy with FOLFOX was delivered. After several months the liver tumors further enlarged and a new pulmonary lesion appeared with an increased serum CEA level. Therefore, chemotherapy with S-1 (120 mg/day) was started, with 2 weeks' administration followed by a one-week drug-free period. Several months later, the liver tumors and tumor makers decreased. S-1 is expected to be an effective agent for the treatment of advanced colon cancer with liver metastases after FOLFIRI and FOLFOX.

Bile duct stone formation around a nylon suture after gastrectomy: a case report.

BACKGROUND: Many cases of choledocholiths formed around sutures and clips used during cholecystectomy have been reported. We describe a case of gallstone formation around a nylon suture after non-biliary surgery. To the best of our knowledge, this is the first report of such a case. CASE PRESENTATION: A 75-year-old Japanese man, who had undergone distal gastrectomy for gastric cancer and reconstruction with the Billroth II method 8 years earlier, presented with gastric discomfort. Abdominal ultrasonography was conducted and we diagnosed cholecysto-choledocholithiasis with dilatation of the intrahepatic bile duct. He underwent cholecystectomy and cholangioduodenostomy for choledocholith removal. Gallstones, which had formed around a nylon suture used during the previous gastrectomy, were found in the bile duct. Sutures of the same material had also been placed on the duodenum. Chemical analysis revealed that the stones were composed of calcium bilirubinate. The patient was discharged on postoperative day 19, and choledocholithiasis has not recurred thus far. CONCLUSION: The findings from this case suggest that standard, non-resorbable sutures used in gastrectomy may be associated with the formation of bile duct stones; therefore, absorbable suture material may be required to avert gallstone formation even in the case of gastrectomy.

Primary malignant melanoma of the esophagus arising from a melanotic lesion: report of a case.

We herein report a case of primary esophageal malignant melanoma in which the development from a preceding benign melanotic lesion and the growing process of the tumor were chronologically observed by serial endoscopic examinations. Biopsy specimens repeatedly taken from the tumor failed to identify the presence of malignant melanoma. A positron emission tomography scan and gross changes of the tumor endoscopically observed were useful for detecting the presence of malignant transformation. The patient eventually died of generalized metastatic disease soon after undergoing an esophagectomy. An early diagnosis may therefore be crucial for improving the treatment outcome of esophageal malignant melanoma. Therefore, esophageal melanotic lesions should be carefully followed up even if biopsy specimens repeatedly show no malignancy.