ABSTRACT
We encountered a case of portal vein thrombosis (PVT) after treatment for portal hypertension due to pancreatic arteriovenous malformation (PAVM). A 75-year-old man was admitted for the treatment of esophageal varices. Diffuse PAVM and aneurysm in the celiac and superior mesenteric arteries were detected via abdominal computed tomography and angiography. Although endoscopical sclerotherapy was performed, PVT was identified after the treatment and variceal bleeding continued. Autopsy was performed and the thrombus and malformation were pathologically confirmed. This case indicates that PVT can be associated with PAVM.
Subject(s)
Arteriovenous Malformations/complications , Pancreas/blood supply , Portal Vein , Venous Thrombosis/complications , Aged , Aneurysm/diagnostic imaging , Angiography , Arteriovenous Malformations/diagnostic imaging , Arteriovenous Malformations/pathology , Celiac Artery/diagnostic imaging , Endoscopy , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/therapy , Fatal Outcome , Hemorrhage/etiology , Humans , Male , Mesenteric Artery, Superior/diagnostic imaging , Pancreas/diagnostic imaging , Phlebography , Portal Vein/diagnostic imaging , Radiography, Abdominal , Sclerotherapy , Tomography, X-Ray Computed , Ultrasonography , Venous Thrombosis/diagnostic imagingABSTRACT
A total of 44 variously halogenated derivatives of aniline, phenol, and thiophenol were subjected to analysis of their inhibitory effect on human cytochrome P450 (CYP) 2E1 to investigate the structure-activity relationships in halogenated phenyl derivatives. The activity of human CYP2E1 of the microsomes from baculovirus-transfected insect cells expressing recombinant human CYP2E1 was determined by measuring quinoline 3-hydroxylation, which was detectable by fluorescence monitoring (Ex=355 nm and Em=460 nm). Diethyldithiocarbamate (DDTC), a specific inhibitor of CYP2E1, potently inhibited quinoline 3-hydroxylation (IC50=8.9 microM). The effects of halogen-substitution in 32 aniline derivatives on the CYP2E1 inhibition can be summarized as follows: more enhancement by chlorine- and bromine-substitution than by fluorine-substitution, more enhancement by para- and metha-halogen-substitution than by ortho-halogen-substitution, and more enhancement by dihalogen-substitution than by mono- and trihalogen-substitution except for trifluorine-substitution. The greatest enhancement of the inhibitory activity was observed in 3,4-dichloroaniline (IC50=8.0 microM) and 3,5-dichloroaniline (IC50=9.2 microM), and their inhibitory activities were very close to that of DDTC. All of the dichlorophenols and dichlorothiophenols were compared with dichloroanilines for CYP2E1 inhibition. Although dichlorothiophenols showed similar or more potent inhibitory activities than dichloroanilines, dichlorophenols showed less inhibitory activities. 3,4-Dichlorothiophenol and 3,5-dichlorothiophenol showed very potent inhibition and their IC50 values were 5.3 and 5.2 microM, respectively. These results suggest that 3,4- and 3,5-dichlorophenyl derivatives may be useful as potent CYP2E1 inhibitors.
