Atherosclerosis is accelerated when it occurs concomitantly with hypertension and hyperlpidemia. We derived a spontaneously hypertensive hyperlipidemic rat (SHHR) by cross-breeding. SHHR represents a good model of vascular degeneration, particularly when the rats are fed a high-fat diet supplemented with a sucrose solution (SHHR-HFDS) . Matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) play important roles in atherosclerosis. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists (thiazolidinediones), such as pioglitazone, decrease plasma MMP-9 expression in type 2 diabetic patients. However, the effects of pioglitazone on MMP-9 and TIMP-1 in atherosclerosis without diabetes are not clear. We investigated the effects of pioglitazone on the activities of MMP-9 and TIMP-1 in the plasma of SHHR-HFDS. Male SHHRs were fed a normal diet for 4 months, and then administered N^G-nitro-L-arginine methyl ester (L-NAME) for 1 month, followed by a high-fat diet (2% cholesterol, 1% cholic acid, 5% coconut oil) and a 15% sucrose solution ad libitum for an additional 2 months. Pioglitazone (3 or 10 mg/kg/day subcutaneously) was co-administered with HFDS for 2 months. Aortic lipid deposition increased clearly in the SHHR-HFDS group at 7 months of age. Pioglitazone decreased aortic lipid deposition and plasma MMP-9 activity, but increased plasma TIMP-1 activity in the SHHR-HFDS group, as compared with the non-treated SHHR-HFDS group. These results suggest that pioglitazone decreases lipid deposition partly by modulating MMP-9 and TIMP-1 activities.

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Nateglinide, a D-phenylalanine derivative, is a non-sulfonylurea insulin secretagogue with a rapid onset and short duration of action. Nateglinideinduced insulin secretion is thought to be triggered by an increase in intracellular calcium (Ca²⁺) caused by binding with the Kir6.2/SUR1 complex and closure of the ATP-sensitive K⁺ (K_ATP) channel, similar to the sulfonylureas. However recently, another pathway for nateglinide-induced insulin secretion has been suggested, which is independent of the K_ATP channel and mediated by intracellular Ca²⁺ release from endoplasmic reticulum. To determine whether nateglinide can stimulate Ca²⁺ release from endoplasmic reticulum, we analyzed intracellular Ca²⁺ mobilization after the addition of nateglinide, using HEK293 cells with inducible expression of exogenous ryanodine receptor type 1 (RyR1) . Nateglinide increased intracellular Ca²⁺ concentration in a dose-dependent manner even in the absence of extracellular Ca²⁺ in cells expressing RyR1, but not in the non-induced cells. These results demonstrate that nateglinide activates RyR1 Ca²⁺ release channels, causing the increase in intracellular Ca²⁺ required to trigger insulin secretion.

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Endoscopic retrograde cholangiopancreatography (ERCP) is a difficult procedure to perform in patients who have undergone Billroth II gastrectomy (B II) . The aims of the present study were to investigate the effect of Braun's anastomosis (BA) on the performance of ERCP and to determine whether the forward-viewing endoscope or side-viewing duodenoscope is the optimal endoscope for performing ERCP in patients who have undergone B II. This was a retrospective review of 52 ERCP procedures conducted in 45 patients who had B II between April 1996 and March 2007. Indications for ERCP included common bile duct stones (N =36; 80%) and tumor stenosis (N = 9 ; 20%) . The success rate for endoscopic approach to the papilla of Vater was significantly higher in those patients without Braun's anastomosis than with Braun's anastomosis (P < 0.0001) . In addition, therapeutic ERCP was performed successfully in more patients without BA than with BA (P=0.0016) . The forward-viewing endoscope was superior to the side-viewing duodenoscope for approaching the papilla of Vater in patients (P = 0.0023) ; however, there was no significant difference between the two types of endoscope for successful therapeutic ERCP (P = 0.2621) . Braun's anastomosis increased the difficulty of performing ERCP using either endoscope and is a major obstacle to conducting ERCP in patients who have undergone B II. The forward-viewing endoscope is preferable for successful ERCP in these patients.

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In the treatment of hemorrhagic gastric ulcer therapeutic endoscopy is providing a remarkable achievement of successful and safe hemostasis. In this communication we compared the efficacy of 3 major endoscopic treatment modalities and their 2 combinations for bleeding gastric ulcer. A total of 476 consecutive patients presenting with bleeding from gastric ulcer were assigned to undergo endoscopic hemostasis by one of the following 4 therapeutic modalities: hemoclip, ethanol injection, heater grid coagulation, and a combination of hemoclip and ethanol injection or that of hemoclip and heater probe. More than 90% of the 476 patients achieved a permanent hemostasis by either of hemoclip, ethanol injection, heater probe, and one of the two combination therapies regardless of the location of visible vessels, stigmata of bleeding, and general health status at presentation. The combination therapy provided a higher success rate, although statistically not significant. Recurrence of bleeding occurred in 13 (4.4%) of 290 patients presenting with mild shock, 11 (9.3%) of 118 patients with moderate shock, and 14 (20.5%) of 68 patients with severe shock before the therapy, retrospectively, indicating a significantly higher rate of rebleeding in patients presenting with a critical general condition. Endoscopic therapy provide successful and safe hemostasis in bleeding gastric ulcer. Combination of hemoclip and ethanol injection or hemoclip and heater probe coagulation may be the most effective. Severe general heath status at presentation increases the risk of rebleeding.

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By investigating the lymph retention state in a rat model we previously demonstrated the reflux flow of cancer cells into the mesenteric lymph vessels and the subsequent presence of these cells in the intestinal wall. Here, as a clinical model of this phenomenon, we analyzed the resected intestines of gastric cancer patients. We examined eight cases of combined intestinal resection for peritoneal metastases of gastric cancer (primary group) and five cases of peritoneal recurrence (recurrent group) . In addition to clinicopathological investigations of the primary gastric cancer, we investigated the pathology of resected intestines according to the area of cancer cell invasion in the intestinal wall. In the primary group, cancer invasion of the intestinal wall was found in the extraserosa in five cases, and in the remaining three cases, cancer invasion had reached the proper muscle layer. In the recurrent group, the cancer invasion had reached every layer of the intestinal wall. The relationship between the area of cancer invasion in the intestinal wall and the peritoneal metastatic foci suggests that cancer cell invasion of the intestinal wall occurs via the lymph system.

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Ovarian granulosa cell tumor (GCT) is a relatively rare neoplasm, with a frequency of 1%-2% of all ovarian neoplasms. Ovarian GCT is categorized as a sex cord stromal tumor and is the most common estrogenproducing ovarian tumor. GCTs are often associated with estrogen-related endometrial changes, ranging from hyperplasia to carcinoma. Herein, we present a case of adult GCT of the ovary with ascites and invasive endometrial carcinoma. A 66-year-old woman presented with a large solid and cystic ovarian tumor. Total hysterectomy and bilateral salpingo-oophorectomy were performed. The cut surface of the tumor had a white-colored solid area and focal necrotic and hemorrhagic areas. Microscopically, a trabecular pattern with edematous stroma, a concomitant microfollicular pattern, and Call-Exner bodies were seen. The pathological diagnosis was adult GCT of the ovary. Immunohistochemical staining was positive for inhibin and vimentin, but negative for cytokeratin (CKAE1 / AE3) . The endometrioid adenocarcinoma (Grade 2) in the uterus showed typical histological findings and immunohistochemical staining. The importance of the present case is that it highlights the fact that GCT are not always low-grade tumors, but can be high-grade malignancies exhibiting invasive growth: the tumor in the present case was large (24.5×18.5×8.0 cm, weighing 2350g), with a considerable amount of ascites and invasive growth of the endometrial carcinoma. That such unusual cases of GCT may occur should be kept in mind when clinical and pathological diagnoses are being made.

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We report an interesting case of microinvasive carcinoma ex pleomorphic adenoma (PA) showing focal recurrence ten months after surgery, which on initial presentation was misdiagnosed as PA with atypia. A 45-year-old woman was admitted to our hospital, presenting with a painless mass in the left cheek that had been present for six years but had increased in size recently. With the clinical diagnosis of benign cheek tumor, a simple tumorectomy was performed. Initially, this tumor was pathologically diagnosed as pleomorphic adenoma (PA) with atypia showing capsular invasion. The patient received no chemotherapy or radiotherapy, but recurrent tumor was found in the left cheek 10 months after surgery, and a second tumorectomy was performed. Pathology of the recurrent tumor revealed PA with atypia or adenocarcinoma not otherwise specified (NOS), and therefore immunohistochemical staining of HER2 / neu was conducted for a differential diagnosis. In atypical foci of the primary tumor and the entire recurrent tumor, atypical cells showed moderately distinct membrane staining of HER2 / neu. This indicated that the primary tumor was microinvasive carcinoma ex PA, and the recurrent tumor was adenocarcinoma NOS. We concluded that immunohistochemical staining of HER2 / neu should be performed to obtain the correct diagnosis in PA cases with atypia.

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