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.     

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.     

Changes in Human Immunodeficiency Virus-related Knowledge and Stigmatizing Attitudes among Korean Adolescents from 2006 to 2011

ObjectivesThis study assessed the prevalence and changes of human immunodeficiency virus (HIV) knowledge and stigmatizing attitudes in 2006, 2008, and 2011.MethodsThree cross-sectional surveys were conducted in 2006, 2008, and 2011. A cross-sectional sample of high school students in Seoul, South Korea was targeted. A self-administered questionnaire measuring general and transmission and discriminatory attitudes was used.ResultsMisconceptions about casual contact were widespread, even though the proportion responding incorrectly decreased significantly over the 5-year period. The respondents in all surveys displayed a high level of discrimination against those with HIV/AIDS in some situations, particularly in the idea of HIV/AIDS making the respondent feel disgusted (63.3% in 2006, 57.5% in 2008, and 52.6% in 2011), avoiding sitting with people with HIV/AIDS (50.6% in 2006, 50.5% in 2008, and 48.5% in 2011), and blaming those with HIV for becoming infected (46.6% in 2006, 42.8% in 2008, and 43.0% in 2011). Even though respondents had a high level of stigmatizing attitudes, the survey showed that the stigma has declined over the 5-year period.ConclusionThe survey results showed that public health policy should recognize that HIV stigmatizing attitudes persist in Korea. This finding has implications for the development of intervention programs focusing on reducing the levels of discrimination.