ABSTRACT
SNX-2112 is a novel Hsp90 inhibitor. The aim of this study was to investigate the pharmacokinetics, tissue distribution, plasma protein binding and excretion profiles of SNX-2112 in Sprague-Dawley rats after a single intravenous injection. The pharmacokinetic properties of SNX-2112 were examined after a single i.v. injection of 2.5, 5, and 10mg/kg to rats, respectively. The tissue distribution and urinary, fecal, and biliary excretion patterns of SNX-2112 were investigated following a single i.v. injection of 10mg/kg. The results suggested that the pharmacokinetic properties of SNX-2112 fitted well into a two-compartment open model with t(1/2ß) values of 9.96±4.32, 10.43±4.06, 10.41±4.38h and area under the curve values of 7.62±1.03, 8.10±0.77, 15.80±1.00(µg/mL) h according to the single doses of 2.5, 5, and 10mg/kg, respectively. Approximately 0.13±0.09% and 3.62±0.77% of SNX-2112 were excreted via the urine and feces within 72h, respectively; 2.59±0.67% was excreted into the bile up to 24h after a single i.v. injection of 10mg/kg. The major elimination route was therefore through excretion in the feces. The binding rate of SNX-2112 with plasma protein was found to be concentration-dependent. In conclusion, this study first provided the full pharmacokinetic characteristics and tissue distribution of SNX-2112, which would be helpful for its clinical regiment design.
Subject(s)
HSP90 Heat-Shock Proteins/antagonists & inhibitors , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Models, Biological , Animals , Area Under Curve , Blood Proteins/metabolism , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Half-Life , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Injections, Intravenous , Male , Protein Binding , Rats , Rats, Sprague-Dawley , Time Factors , Tissue DistributionABSTRACT
AIM: Clinical application and potential complication of percutaneous transsplenic varices embolization (PTSVE) of esophageal or gastrio-fundal varices in patients with hepatocellular carcinoma (HCC) complicated with portal vein cancerous thrombosis (PVCT). METHODS: 18 patients with HCC complicated with PVCT and esophageal or gastrio-fundal varices who underwent PTSVE were collected. The rate of success, complication, mortality of the procedure and postoperative complication were recorded and analyzed. RESULTS: PTSVE were successfully performed in 16 of 18 cases, and the rate of success was 89%. After therapy erythrocyte counts decreased in all of the natunts. 5 of patients needed blood transfusion, 2 patients required surgical intervention because of and 11 patients with ascites were alleviated by diuresis. Among these 18 patients, the procedure-related mortality was 11% (2/18), one died of acute hepatic failure on the forth day after procedure, another died of acute renal failure on the fifth day. The patients were follow up for 1-12 mon exceptone. 13 of them died of their tumors but none of them experienced variceal bleeding. CONCLUSION: PTSVE is a relatively safe and effective method to treat esophageal or gastrio-fundal varices in HCC patients with PVCT when percutaneous transhepatic varices embolization (PTHVE) of varices is impossible.
Subject(s)
Embolization, Therapeutic , Esophageal and Gastric Varices/therapy , Adult , Aged , Carcinoma, Hepatocellular/complications , Esophageal and Gastric Varices/complications , Female , Humans , Liver Neoplasms/complications , Male , Middle Aged , Portal Vein , Venous Thrombosis/complicationsABSTRACT
Magdala Red (MR) binding to protein causes a decrease in the fluorescence intensity of MR at 556 nm. Based on this, a new quantitative determination method for proteins is developed. The linear range of this assay is 0.1-4.0 microg ml(-1) of Bovine Serum albumin (BSA). The measurements can be made easily on a common fluorimeter. The reaction between MR and proteins is completed in 1 min, and the fluorescence intensity is stable for at least 2 h. There is little or no interference from amino acids and most metal ions. The proposed method has been applied to the determination of protein in milk powder and soybean milk powder and the results are in agreement with the results by the other methods.
Subject(s)
Fluorescent Dyes , Proteins/analysis , Animals , Cattle , Humans , Hydrogen-Ion Concentration , Molecular Structure , Naphthalenes/chemistry , Pyrazines/chemistry , Spectrometry, Fluorescence/methodsABSTRACT
Harris tow-stage left anterior coronary ligation was performed in anesthetized dogs. After twenty hours, severe ventricular arrhythmias were recorded under conscious state. Cumulative intravenous injections of guanfu base A, a new alkaloid isolated from the tuber of Aconitum coreanum in China, from 10 to 40 mg.kg-1 produced remarkable antiarrhythmic effect lasting over 30 min and a moderate reduction of heart rate. The P-R interval, QRS complex and Q-T interval of the sinus rhythm were not significantly altered. The antiarrhythmic potency of guanfu base A in this model was found to be about one third that of quinidine.
