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 role of intraoperative monitoring of oculomotor and trochlear nuclei -safe entry zone to tegmental lesions.

OBJECTIVE: A safe entry zone to tegmental lesions was identified based on intraoperative electrophysiological findings, the compound muscle action potentials (CMAP) from the extraocular muscles, and anatomic considerations. This entry zone is bordered caudally by the intramesencephalic path of the trochlear, laterally by the spinothalamic tract, and rostrally by the caudal margin of the brachium of the superior colliculus. METHODS: Four intrinsic midbrain lesions were operated upon via the safe entry zone using the infratentorial paramedian supracerebellar approach. All lesions involved the tegmentum and included an anaplastic astrocytoma, a metastatic brain tumor, a radiation necrosis, and a cavernous angioma. CMAP were bilaterally monitored from the inferior recti (for oculomotor function) and superior oblique (for trochlear nerve function) muscles. RESULTS: In three of four cases, CMAP related to the oculomotor nerve were obtained upon stimulation at the cavity wall after removal of the tumor. Stimulation at the surface of the quadrigeminal plate, however, did not cause any CMAP response. Using this monitoring as an indicator, the lesions were totally removed. CONCLUSIONS: In the surgery of tegmental lesions, CMAP monitoring from extraocular muscles is particularly helpful to prevent damage to crucial neural structures during removal of intrinsic lesions, but less so to select the site of the medullary incision. The approach via the lateral part of the colliculi is considered to be a safe route to approach the tegmental lesions.     

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.     

Gliomatosis peritonei

Gliomatosis peritonei, the miliary implants of mature glial tissues on the peritoneum or omentum, is a rare complication of solid ovarian teratoma. Our case is reported and 38 previously reported cases are reviewed. The grade of the primary tumors varied from grade 0 to grade 3. Only five cases were composed entirely of mature tissues. Five of the 39 patients died. Despite of varied therapy, the rest of the patients were alive from 3 months to 38 years later. Inspite of intraperitoneal implants, the prognosis in patients with these tumors is good, irrespective of the mode of therapy. On the basis of this study, we recommended a conservative therapy for the primary tumor and therapy for the implants is not required.     

Immunohistochemical Detection of Porcine Teschovirus Antigen in the Formalin‐fixed Paraffin‐embedded Specimens from Pigs Experimentally Infected with Porcine Teschovirus

Porcine teschovirus (PTV) antigens were detected by a streptavidin‐biotin complex method in formalin‐fixed paraffin‐embedded tissues of 3‐week‐old pigs that had been inoculated intravenously with PTV Talfan strain. PTV antigens were detected in cytoplasm of nerve cells, glial cells and endothelial cells in the cerebellar nuclei, the grey matter of the midbrain, pons and medulla oblongata and the ventral horn of the spinal cord and of ganglion cells in the spinal ganglion corresponding to those lesions characterized as non‐suppurative encephalomyelitis and ganglionitis. The results of this study suggest that nerve cells of the brain stem and spinal cord and ganglion cells of the spinal ganglion permit PTV replication and represent the main target cell population of PTV. This is the first study to demonstrate PTV antigen by immunohistochemistry in formalin‐fixed paraffin‐embedded tissue specimens from pigs infected with PTV.     

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.