Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

The prognostic value of E-cadherin, α-, β- and γ-catenin in bladder cancer patients who underwent radical cystectomy

OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer.     

Leukotriene B4 production in children with steroid-responsive nephrotic syndrome

Leukotriene B₄ (LTB₄) production in polymorphonuclear leucocytes (PMN) was examined in ten children with steroid-responsive nephrotic syndrome (SRNS) before, during, and after steroid administration. Comparison of LTB₄ production was made in 14 children with non-inflammatory disease who were not receiving steroid therapy. No significant change was noted in PMN LTB₄ biosynthesis in children with SRNS throughout any phase of the disease. Furthermore, there was no significant difference in LTB₄ biosynthesis in PMN between SRNS patients before steroid therapy and patients with non-inflammatory disease. These findings suggest that inhibition of LTB₄ production is not involved in the mechanism underlying steroid action in SRNS.     

Surgical management of endocrine tumor of the pancreas in Japan

Endocrine tumor of the pancreas is potentially malignant. A multicenter analysis of these tumors was conducted to clarity the present status of their surgical management and the subsequent long-term surgical results. The Japan pancreatoduodenectomy (JPD) study group carried out the study; 368 patients were enrolled and variables related to tumor characteristics, surgery, and survival were retrospectively analyzed. There were 222 patients with functioning tumor and 143 patients with nonfunctioning tumor. Malignant tumor was found in 140 of 368 (38%) of the patients, and 63/140 (45%) of these patients had metastatic lesion; the most common site of the metastasis was liver 34/136 (25%), followed by regional lymph nodes 26/136 (19%). Pancreatic resection was performed in 91% of patients with nonfunctional tumor and in 83% of those with malignant tumor, and 73% of the pancreatic resections were done with lymph node dissection. The overall 5-year actuarial survival rate was 76% in patients with malignant tumor. The actuarial 5-year survival rate was 93% in the patients without metastasis and 83% in patients who received curative resection. Multivariate analysis showed that the presence or absence of synchronous metastasis was the sole significant prognostic factor. The results suggest that: (i) malignant endocrine tumor of the pancreas is a curable malignancy when pancreatic resection with lymph node dissection is adopted and (ii) that synchronous metastasis is the dominant prognostic factor. This study was carried out as a group project. The authors' institutions are as follows     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.     

Leukocytosis and low serum IgA in workers exposed to the epoxy compound,t-methyl-3-phenylglycidate

Summary Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varing degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.     

A case of serous cystadenoma of the pancreas with focal malignant changes

Summary We present a serous cystadenoma of the pancreas with focal malignant changes, and describe its characteristic histological features. On gross examination, a tumor was present on the anterior surface of the body of the pancreas and measured approx 25×25⋻20, mm. Microscopically, most tumor cells showed the typical histological features of serous cystadenoma, characterized by a microcystic architecture and glycogenrich cells with a uniform and bland appearance. However, in some areas, a tendency to papillary structures with fibrovascular cores was noted. These papillary lesions were composed mainly of nonmucinous, glycogen-poor epithelial cells, the nuclei of which showed a mild atypia. In addition, vascular and perivascular invasion was focally observed. However, there was no clinical evidence of local or distant metastasis. From these findings, we diagnosed this lesion as a serous cystadenoma of the pancreas with focal malignant changes rather than a serous cystadenocarcinoma of the pancreas.