Aniracetam,a Pyrrolidinone-type Cognition Enhancer,Attenuates the Hydroxyl Free Radical Formation in the Brain of Mice with Brain Ischaemia

We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (· OH) during ischaemia-reperfusion of mouse brain. The fact that brain ischaemia for 40 min followed by reperfusion increased ·OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxy-benzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring ·OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg^?1 showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mg kg^?1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg^?1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.     

High-performance Liquid Chromatographic Determination of Trazodone and 1-m-Chlorophenylpiperazine with Ultraviolet and Electrochemical Detector

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C₈ reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100–2000 ng mL^?1 and for m-CPP in the concentration range 5–100 ng mL^?1. The recoveries of trazodone and m-CPP added to plasma were 81·0–84·2 and 68·0–73·2%, respectively, with coefficients of variation of less than 7·3 and 8·2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.     

Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats†

The aim of the present study was to clarify whether bile acids influence chemiluminescence (CL) in the liver in vivo. Hepatic CL was determined on the surface of the liver of anaesthetized rats by using a photon counter. In normal rats, hepatic CL was significantly decreased 30 min after enteral administration of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA), but returned to its initial level 3 h later, after part of the CDCA administered was metabolized. Ursodeoxycholic acid (UDCA) and cholic acid had no effect on CL. In contrast, hepatic CL was markedly increased 30 min after CDCA or DCA administration in rats given either buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, or diethyldithiocarbamate (DDC), an inhibitor of both superoxide dismutase and glutathione peroxidase. Chenodeoxycholic acid further increased the CL of BSO- or DDC-treated rats during inhalation of oxygen via a tracheal cannula. Coadministration of UDCA eliminated the effects of CDCA on the hepatic CL of normal and BSO- or DDC-treated rats with or without oxygen inhalation. We conclude that cytotoxic bile acids, such as CDCA, increase CL in the antioxidants-depleted or oxidative-stressed liver in vivc, but that UDCA prevents CDCA from developing CL.     

Current Density Distribution by Ring and Diagonally Arranged Half‐Ring Electrodes in Bipolar and Overlapping Biphasic Impulse Stimulation

Background: We have studied the acute and long‐term efficacy of overlapping biphasic impulse (OLBI) stimulation for atrial pacing with VDD pacemakers and demonstrated the feasibility of DDD pacing in OLBI with diagonally arranged half‐ring (Half‐Ring) electrodes. We made two three‐dimensional computational analysis models to verify our clinical studies. Methods and Results: Model I was composed of a heart, a pacemaker, and a human body. Model II was a cube with dimensions of 20 by 20 by 20 mm quarried from Model I for the detailed study of current density distributions. Laplace's equation was solved using the finite element method and the current density J was calculated. For Model I, the distal and proximal voltages were ?10 V, 0 V in bipolar and ?5 V, +5 V in OLBI, using Ring electrodes. In Model II, the actual measurements of electrode impedances obtained from the clinical study (1,180 Ω for Ring and 630 Ω for Half‐Ring) were added to the analysis conditions. Model I showed that OLBI produced more concentrated current density distributions than those by bipolar. According to Model II, at the atrial myocardium position current density produced by Half‐Ring was larger than that by Ring electrodes, 70 μA/mm² versus 30 μA/mm² in OLBI configuration. It also indicated that even if electrode impedances were equal between Half‐Ring and Ring electrodes, the maximum current density produced by Half‐Ring would be greater than that by Ring electrodes. Conclusions: It was considered that OLBI configuration with Half‐Ring electrodes provides more effective current density distributions. (PACE 2010; 33:1063–1073)     

Utility of immunohistochemical detection of prostate-specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions

BACKGROUND: Human prostate-specific Ets (hPSE) belongs to the Ets family. It regulates the proliferation, differentiation, and development of prostate epithelial cells. A recent study showed that hPSE can be detected in normal glands but not in cell lines established from prostate cancer (PCA), suggesting a translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical detection of hPSE could therefore be another method of differential diagnosis of PCA from other proliferative conditions in the prostate. METHODS: An immunohistochemical detection of hPSE was carried out on the whole mounted prostatectomy specimen obtained from 19 cases with PCA. RESULTS: Basal and secretory luminar cells showed a diffuse cytoplasmic staining for hPSE in normal glands, hyperplastic glands, and prostate intraepithelial neoplasia lesions. Whereas approximately 30% of PCA lesions showed a negative staining for hPSE, the positive rate for hPSE between PCA and benign glands or prostate intraepithelial neoplasia (PIN), was statistically significant (P < 0.05). Staining intensities in normal glands, hyperplastic glands, and PIN lesions were similar, but generally stronger than those in PCA lesions. CONCLUSIONS: Negative immunoreactivity for hPSE strongly suggests malignancy in the prostate glands. Decreased immunoreactivities of glands for hPSE could suggest PCA.     

Idiopathic retroperitoneal fibrosis associated with IgG4-positive-plasmacyte infiltrations and idiopathic chronic pancreatitis

Idiopathic retroperitoneal fibrosis (IRPF) is an inflammatory fibrosclerosing condition, leading to renal failure by obstruction of the ureters. Idiopathic chronic pancreatitis associated with marked inflammatory infiltrates has recently been referred to as autoimmune pancreatitis (AIP), and infiltrating plasmacytes carrying immunoglobulin-gamma type 4 (IgG4) are relevant to its pathogenesis. The case is described herein of IRPF associated with subclinical pancreatitis that was most probably AIP in a 70-year-old man. Biopsy specimens of the retroperitoneal pseudotumor revealed a marked lymphoplasmacytic infiltration with dense fibrosis. Infiltrating plasma cells were immunoreactive for anti-IgG4 antibodies. Subsequent systemic examinations showed an extremely elevated serum IgG4 level and pancreatitis concordant with AIP. Following oral steroid administration, the serum IgG4 level normalized, although the appearance of the pseudotumor did not alter. Some AIP cases have been associated with idiopathic fibrosclerosing disorders including IRPF, but histological evidence of IgG4-related IRPF has rarely been provided.     

Laparoscopic cholecystectomy in the elderly: Analysis of pre-operative risk factors and postoperative complications

A retrospective study was conducted of two groups of patients over (group 1, n= 57) and under (group 2, n= 655) the age of 70 years who underwent laparoscopic cholecystectomy (LC). The pre-operative physical status and systemic complications, operation time, postoperative complications, postoperative hospital stay and other clinical features of the two groups were compared. The incidence of pre-operative complications in group 1 was significantly higher than that in group 2 (P < 0.05). Postoperatively no severe complication was found in any patient. Group 1 showed significantly prolonged operation time and postoperative hospital stay compared with group 2 (P < 0.05). The difference between the groups in the intra-operative treatment time and postoperative treatment is attributed to the greater prevalence of common bile duct stone in group 1 as there was little difference between the groups in the postoperative recovery after exclusion of these patients. No pulmonary complications, which are associated with LC, were observed; the postprocedure pain was slight and the period of bedrest was short. If complications associated with pneumoperitoneum can be prevented, this surgery is an excellent measure to improve the quality of life of even elderly patients with cholecystolithiasis.     

Rare case of aggressive angiomyxoma presenting as a retrovesical tumor

Aggressive angiomyxoma (AAM) is a rare mesenchymal benign tumor that preferentially involves the pelvic and perineal regions in relatively young females. We report here a rare case of AAM presenting as a retrovesical tumor in a male patient. A 59-year-old man undergoing abdominal ultrasound examination because of benign prostatic hyperplasia was found to have a retrovesical mass. Computed tomography and magnetic resonance imaging of the pelvis showed the retrovesical tumor to be 7.4 x 6.7 cm. The tumor was resected, and diagnosed histopathologically as AAM. The patient showed no recurrence 26 months after resection. Although the majority of retrovesical tumors are considered to be sarcoma or neurogenic tumor, AAM should also be recognized as a differential diagnosis.