ABSTRACT
We report here that pregnenolonyl-α-glucoside (2), a steryl glycoside synthesized directly from pregnenolone and glucose via a consecutive multienzyme-catalyzed process, exhibits marked dose-dependent cytotoxic activity against HT29, AGS, and ES-2 cells with IC50 values of 23.5 to 50.9 µM. An in vitro CYP17A1 binding pattern assay and protein-ligand docking model support that 2, like abiraterone, binds in the active site heme iron pocket of CYP17A1.
Subject(s)
Antineoplastic Agents/pharmacology , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Glucosides/pharmacology , Pregnenolone/analogs & derivatives , Pregnenolone/pharmacology , Androstenes/metabolism , Androstenes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Bacteria/enzymology , Catalytic Domain , Cell Line, Tumor , Cytochrome P-450 Enzyme Inhibitors/chemistry , Cytochrome P-450 Enzyme Inhibitors/metabolism , Glucosides/chemical synthesis , Glucosides/metabolism , Glycosylation , HEK293 Cells , Humans , Molecular Docking Simulation , Pregnenolone/metabolism , Protein BindingABSTRACT
OBJECTIVE: To compare the accuracy of indirect mutidetector row computed tomographic (MDCT) venography with lower extremity venous sonography for the diagnosis of femoropopliteal deep venous thrombosis (DVT), and to determine the frequency and location of DVT at MDCT venography. MATERIALS AND METHODS: Twenty-six consecutive patients suspected of having pulmonary embolism (PE) underwent both combined MDCT venography and MDCT pulmonary angiography and lower extremity venous sonography. Indirect MDCT venography was acquired from the upper calves to the mid-abdomen following MDCT pulmonary angiography. The CT venographic findings were compared with those of sonography for the diagnosis of femoropopliteal DVT. All CT scans were also reviewed for the frequency and location of DVT. RESULTS: Indirect MDCT venography disclosed DVT in 19 patients, and 12 of whom also had PE. Seventeen patients with thrombosis in the femoropopliteal veins were identified in both indirect MDCT venography and sonography. The sensitivity and specificity of indirect MDCT venography for femoropopliteal DVT, as compared with sonography, were both 100%. In one patient DVT in the superficial femoral vein was detected using only indirect MDCT venography. MDCT venography also showed superior extension of femoropopliteal DVT to the inferior vena cava and iliac veins in four patients and thrombosis isolated to the inferior vena cava and common iliac vein thrombosis in one patient. CONCLUSIONS: Indirect MDCT venography is as accurate as sonography in the diagnosis of femoropopliteal DVT. MDCT venography can further reveal thrombus in large pelvis veins and the inferior vena cava, an important advantage over sonographic screening for DVT.
Subject(s)
Ultrasonography, Doppler/methods , Venous Thrombosis/diagnostic imaging , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Phlebography/methods , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Tomography, X-Ray Computed/methodsABSTRACT
The purpose of this study is to evaluate the usefulness of combined computed tomography venography and pulmonary angiography (CTVPA) in the diagnosis of venous thromboembolic (VTE) disease in the emergency department (ED). CTVPA images and clinical data of 73 nonselected patients with suspected pulmonary embolism (PE) and/or deep venous thrombosis (DVT) were retrospectively assessed. CTVPA correctly identified 33 of 34 patients with VTE disease, including 7 patients with PE alone, 11 patients with DVT alone, and 16 patients with both PE and DVT. Among the 27 patients with DVT, CTVPA disclosed thrombosis involving the abdominal and pelvic veins in 4 patients, and isolating to the inferior vena cava and iliac vein in one patient. CTVPA showed high accuracy in the diagnosis of both PE and DVT, in comparison with lower extremity venous sonography and ventilation-perfusion scintigraphy. In 26 (66%) of the 39 patients without of evidence VTE, CTVPA provided important ancillary information that suggests additional or alternative diagnoses. CTVPA is therefore an appropriate single diagnostic tool for evaluation VTE disease in the ED.