Imaging diagnosis of 12 patients with hepatic tuberculosis

AIM: To assess CT, MR manifestations and their diagnostic value in hepatic tuberculosis. METHODS: CT findings in 12 cases and MR findings in 4 cases of hepatic tuberculosis proved by surgery or biopsywere retrospectively analyzed. RESULTS: (1) CT findings: One case of serohepatic type of hepatic tuberculosis had multiple-nodular lesions in the subcapsule of liver. Parenchymal type was found in 10 cases, including multiple, miliary, micronodular and low-density lesions with miliary calcifications in 2 cases; singular, low-density mass with multiple flecked calcifications in 3 cases; multiple cystic lesions in i case; multiple micronodular and low-density lesions fusing into multiloculated cystic mass or 'cluser' sign in 3 cases; and singular, macronodular and low-density lesion with multiple miliary calcifications in 1 case. One case of tuberculous cholangitis showed marked dilated intrahepatic ducts with multiple flecked calcifications in the porta hepatis. (2) MR findings in 4 cases were hypointense on both Tl-weighted imagings and T2-weighted imagings in one case, hypointense on Tl-weighted imagings and hyperintense on T2-weighted imagings in 3 cases. Enhanced MR in 3 cases was slightly shown peripheral enhancementor with multilocular enhancement. CONCLUSION: Various types of hepatic tuberculosis have different imaging findings, and typical CT and MR findingscan suggest the diagnosis.

A comprehensive cardiotoxicity assay by combining high-throughput multiple ion channel screening with human cardiomyocyte-based action potential validation

OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based validation.METHODS Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch clamping.Subsequently,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch clamping.RESULTS We have tested the cardiotoxicity of monomers extracted from various medical herbs.Mitragynine is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East Asia.As a popular stimulant,it has been associated with a number of acute fatal incidences.We observed a typical torsadogenic hazard of mitragynine.It exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion channels.Moreover,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low cardiotoxicity.It exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·L-1.At 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in hPSC-CMs.CONCLUSION We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs validation.This new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potential pro-arrhythmic risk.