Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

Optimum ratio of distraction in double level tibial lengthening

The authors reviewed 43 double level tibial lengthenings by Ilizarov technique in 34 consecutive patients (6-31 years old), and investigated the factors affecting regenerate bone healing to determine the optimum ratio of distraction rate or magnitude of lengthening at the proximal and distal osteotomy sites. Length gain averaged 6.1 cm (range, 2.5-12.3 cm), equivalent to a 28% increase of the segment. The variables investigated included age, gender, concomitant deformity correction, etiology, and the amount of length gain. The healing index averaged 1.8 months per centimeter proximally and 2.8 months per centimeter distally. Age and the amount of length gain affected the healing index at proximal and distal lengthening sites. However, the proximal to distal healing index ratio, which averaged 0.72, was not affected by any parameters investigated. This study suggests that to minimize external fixation treatment time, the distraction rate, or amount of length gain, of the distal osteotomy site should be approximately 3/4 that of the proximal site in the double level tibial lengthening.     

Analysis of chromosome aberrations in nuclear-power-plant workers considering the lifetime of lymphocytes

PURPOSE: To analyse chromosome aberrations in nuclear-power-plant workers taking account of the mean lifetime of lymphocytes (MLTL). MATERIALS AND METHODS: Analysis of chromosome aberrations was performed on peripheral lymphocytes from 395 nuclear-power-plant workers and 135 controls. An equivalent acute dose (EAD) was calculated utilizing MLTL values of either 4.3 or 10 years. RESULTS: Using an MLTL value of 10 years produced an EAD range of 0.O1 mSv -182mSv(mean 46.6mSv), while using an MLTL, of 4.3 years produced results ranging from 0.01 mSv to 86.2 mSv (mean 23.4 mSv). A significant increase of chromosome-type exchange by the equivalent acute dose was observed using an MLTL of either 10 or 4.3 years when including the control in the analysis, but a significant increase was not seen when only the exposed was considered. A significant increase of chromosome-type deletion by EAD was seen even when only the exposed group was considered. CONCLUSIONS: EAD values based on an MLTL of either 4.3 or 10 years, as well as cumulative dose, showed no significant association with chromosome aberrations, when radiation workers only were analysed. The narrow dose range examined in this study might have contributed to this finding.     

Comparing MR imaging and CT in the staging of gastric carcinoma

OBJECTIVE: The purpose of this study was to assess the usefulness of breath-hold two-dimensional (2D) fast low-angle shot (FLASH) and T2-weighted turbo spin-echo fast MR imaging compared with helical CT in the staging of gastric carcinoma. SUBJECTS AND METHODS: Thirty patients with gastric carcinoma underwent preoperative MR imaging and helical CT. MR imaging at 1.5 T was performed immediately after the intramuscular injection of scopolamine and the oral administration of water or effervescent granules. Breath-hold 2D FLASH T1-weighted images in all three planes, turbo spin-echo T2-weighted axial images, and gadolinium-enhanced fat-suppressed 2D FLASH axial images were included. Helical CT was performed 60 sec after initiation of i.v. contrast medium injection (2.5-3 ml/sec). Two groups of two radiologists each independently analyzed the MR and helical CT findings, and these results were compared with the pathologic findings. RESULTS: For T staging, MR imaging accuracy was higher than that of helical CT (73.3% and 66.7%, respectively); however, the accuracies of the two methods were not significantly different from each other (McNemar test, p > 0.05). Overstaging was noted in 6.7% of cases with MR imaging and 10% with helical CT. Understaging was noted in 20% of cases with MR imaging and 23.3% with helical CT. For N staging, the accuracies of MR imaging and helical CT were 55% and 58.6%, respectively, with no statistical significance (overstaging, 10% and 6.9%; understaging, 34.5% and 34.5%, respectively). CONCLUSION: MR imaging was comparable to helical CT in the T and N staging of gastric cancer.     

Tectorigenin, an isoflavone of Pueraria thunbergiana Benth., induces differentiation and apoptosis in human promyelocytic leukemia HL-60 cells

Cytotoxic effects of six isoflavonoids, tectorigenin, glycitein, tectoridin, glycitin, 6'-O-xylosyltectoridin, and 6'-O-xylosylglycitin isolated from the flower of Pueraria thunbergiana Benth. together with genistein, a known differentiation and apoptosis inducer, were examined. Among these isoflavonoids, tectorigenin and genistein exhibited cytotoxicity against various human cancer cells; glycitein showed only mild cytotoxicity. These results suggest that the isoflavone structure and 5-hydroxyl group are crucial for the cytotoxic properties and that glycosides are inactive. Moreover, tectorigenin induced differentiation of human promyelocytic leukemia HL-60 cells to granulocytes and monocytes/macrophages, and caused apoptotic changes of DNA in the cells, as did genistein. Tectorigenin also inhibited autophosphorylation of epidermal growth factor (EGF) receptor by EGF and decreased the expression of Bcl-2 protein, with less activity than genistein. From these results, tectorigenin may be a possible therapeutic agent for leukemia.