Microscopic anatomy of the brain–meningioma interface

We analyzed the relation between meningioma and the brain in 50 surgical cases. So-called capsule formation was seen in 20 meningiomas, of which 13 were categorized as thin and 7 as thick. In 21 meningiomas the arachnoid membrane was intact, and 10 meningiomas had no underlying arachnoid membrane. The other 19 tumors showed partial disruption of the arachnoid membrane. The degree of arachnoid disruption correlated with the tumor grade, perifocal edema, pial blood supply on angiography, and tumor size. The existence of brain invasion correlated with the tumor grade and partially with tumor size. In case of invasive tumor, GFAP-positive cells were found deep in the tumor, usually in contact with blood vessels. The axons in gliotic brain often showed degenerative changes such as ballooning or varicose swelling. Meningiomas were usually demarcated by a basement membrane that was collagen type 4 (Col4)-positive. However, atypical and anaplastic meningiomas usually lacked Col4 staining at the interface. In two benign meningiomas that looked like an invasive growth, Col4 staining was seen above the brain. A pia mater-like structure covered the tumor surface in both cases. We could not demonstrate a relation between the expression of matrix metalloproteinase (MMP)-2 or MMP-9 and arachnoid disruption or brain invasion.     

Correlation between expression of orotate phosphoribosyl transferase and 5-fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer tissue

Background. 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective. Aim of the Study. This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity. Methods. Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated. Results. The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group (p<0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%. Conclusions. The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy.     

QT PRODACT: evaluation of the potential of compounds to cause QT interval prolongation by action potential assays using guinea-pig papillary muscles

Certain compounds that prolong QT interval in humans have little or no effect on action-potential (AP) duration used traditionally, but they inhibit rapidly-activated-delayed-rectifier potassium currents (IKr) and/or human ether-a-go-go-related gene (hERG) currents. In this study using isolated guinea-pig papillary muscles, we investigated whether new parameters in AP assays can detect the inhibitory effects of various compounds on IKr and/or hERG currents with high sensitivity. The difference in AP duration between 60% and 30% repolarization, 90% and 60% repolarization, and 90% and 30% repolarization (APD30-60, APD60-90, and APD30-90, respectively) were calculated as the new parameters. All the 15 IKr and/or hERG current inhibitors that have been reported (9 compounds) or not reported (6 compounds) to inhibit calcium currents prolonged APD30-60, APD60-90, and/or APD30-90; and 8 of the 15 inhibitors prolonged APD30-60, APD60-90, and/or APD30-90 more potently than APD90. The APD30-60, APD60-90, and APD30-90 measurements revealed no difference in sensitivity when evaluating the effects of the IKr and/or hERG current inhibitors on the three parameters. On the other hand, compounds with little or no effect on hERG currents had no effect on APD30-60, APD60-90, or APD30-90. Therefore, it is concluded that in AP assays using isolated guinea-pig papillary muscles, APD30-60, APD60-90, and APD30-90 are useful indexes for evaluating the inhibitory effects of compounds including mixed ion-channel blockers on IKr and/or hERG currents.     

Rapid and simple determination of epoxyeicosatrienoic acids in rabbit renal artery by reversed-phase HPLC with fluorescence detection

A liquid chromatographic method with fluorescence detection coupled with a solid-phase extraction was applied to the rapid determination of epoxyeicosatrienoic acids (EETs) in the rabbit renal artery. The EETs were extracted with an acetonitrile from renal artery homogenate and concentrated by a solid-phase extraction method. The concentrated EETs were reacted directly with a 6, 7-dimethoxy-1-methyl-2 (1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ) hydrazide and separated by a reversed-phase HPLC with eluting a combination of a step-wise and a gradient of a mixture of methanol and water. The content of EETs in the renal arteries was significantly greater in the 0.5% cholesterol fed rabbits than in control rabbits. It is suggested that hyperchlesterolemia increases the production of EETs in the rabbit renal artery.     

Estimation of detection limit from slope of B/B0 in competitive ELISA

A method has been proposed for determining the detection limit (L(D)) from the slope of a semilogarithmic plot of a B/B(0) curve in competitive enzyme linked immunosorbent assay (ELISA). As an application, this paper describes a graphic determination of L(D) from analogue data in the literature. The L(D) obtained corresponds to the concentration at which the relative standard deviation of concentration estimates is 30%.     

Adrenomedullin causes coronary vasodilation in humans: effects of inhibition of nitric oxide synthesis

Experimental studies have shown that adrenomedullin (AM) causes vasodilation, in part, mediated by endothelium-derived nitric oxide (NO). However, it remains to be clarified how NO is involved in AM-induced coronary vasoreactivity in humans. We examined whether NO contributes to the vasodilatory effects of adrenomedullin on human coronary arteries. In 10 patients with angiographically normal coronary arteries, adrenomedullin (low dose: 1 ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N-monomethyl-L-arginine (L-NMMA, 40 micromol/min for 5 min), an NO synthase inhibitor. Coronary diameter and coronary blood flow (CBF) were evaluated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to adrenomedullin were expressed as percent changes from baseline values. Adrenomedullin at a high dose dilated coronary arteries (3.7+/-0.5%, P<0.001). Adrenomedullin increased the coronary blood flow at both doses (low: 55.7+/-13.9%, P<0.01; high: 48.8+/-9.8%, P<0.001). After the infusion of L-NMMA, adrenomedullin-induced coronary vasodilation and increase in coronary blood flow were attenuated. These findings suggest that adrenomedullin dilates human coronary arteries through an increase in NO production, at least in part.     

Rotational acetabular osteotomy for osteonecrosis with collapse of the femoral head in young patients

BACKGROUND: While rotational acetabular osteotomy has been reported to be successful for the treatment of osteoarthritis of the dysplastic hip, little is known about its efficacy in the treatment of osteonecrosis of the femoral head. METHODS: We retrospectively reviewed the results for a consecutive series of twenty-one patients (twenty-five hips) who had undergone rotational acetabular osteotomy between 1995 and 2001 for the treatment of extensive osteonecrosis of the femoral head associated with collapse. All but two of the patients had a history of steroid therapy as part of a treatment regimen for various diseases. At the time of surgery, the mean age of the five men and sixteen women was 29.0 years. The mean duration of follow-up was forty-nine months. No patient was lost to follow-up. The lesions were classified according to the staging system described by Steinberg et al., and the extent of necrosis was measured with use of the criteria described by Kerboul et al. Clinical evaluation was performed with use of the scoring system of Merle d'Aubigne and Postel. Radiographic evaluation was performed with use of yearly serial anteroposterior and lateral plain radiographs. RESULTS: The mean Merle d'Aubigne and Postel score improved from 11.3 points preoperatively to 14.9 points at the time of the final follow-up (p < 0.001). The mean pain score improved from 3.0 to 5.6 points (p < 0.001). However, the mean mobility score was 5.3 points preoperatively but only 4.9 points postoperatively (p = 0.1). All of the osteotomy sites showed radiographic evidence of osseous union at the time of the latest follow-up. Collapse of the femoral head progressed in seven hips, but in six of these hips the change in the extent of collapse was <2 mm. CONCLUSIONS: In the present study of young patients with extensive osteonecrosis and collapse of the femoral head, rotational acetabular osteotomy was associated with symptomatic relief and absence of substantial collapse of the femoral head at the time of early to intermediate-term follow-up.     

Effect of fasting on methionine adenosyltransferase expression and the methionine cycle in the mouse liver

The effect of fasting on mouse liver methionine adenosyltransferase (MAT I/ III) expression and the regulation of methionine metabolism were investigated. The mRNA level, protein level, and activity of MAT I/III were increased by fasting for 10 or 16 h. In spite of the increase of MAT I/III activity, S-adenosylmethionine, the product of methionine due to MAT I/III, decreased. S-Adenosylhomocysteine, which is made from S-adenosylmethionine by its coupling to methyltransferase, increased as a result of fasting for 16 h. These results suggest that the total methylation reactions using S-adenosylmethionine are stimulated in the fasting mouse liver. However, the DNA methylation level was not changed by fasting for 16 h. Glutathione, which is made by the transsulfuration pathway from homocysteine, decreased due to fasting. Regulation of supplementation of S-adenosylmethionine may occur in the fasting mouse because MAT I/III activity increases and the flow to glutathione is decreased.