ABSTRACT
A new sphere-mapping algorithm called sector mapping is introduced to map sector images to the sphere of an eyeball. The proposed sector-mapping algorithm is evaluated and compared with the plane-mapping algorithm adopted in previous work. A simulation that maps an image of concentric circles to the sphere of the eyeball and an analysis of the difference in distance between neighboring points in a plane and sector were used to compare the two mapping algorithms. A three-dimensional model of a whole retina with clear retinal detachment was generated using the Visualization Toolkit software. A comparison of the mapping results shows that the central part of the retina near the optic disc is stretched and its edges are compressed when the plane-mapping algorithm is used. A better mapping result is obtained by the sector-mapping algorithm than by the plane-mapping algorithm in both the simulation results and real clinical retinal detachment three-dimensional reconstruction.
Subject(s)
Retinal Detachment/diagnostic imaging , Algorithms , HumansABSTRACT
1. Rutaecarpine, a quinolone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, is one of the main active components used in a variety of clinical applications, including the treatment of hypertension and arrhythmia. However, its hepatotoxicity has also been reported in recent years. 2. Reactive metabolites (RMs) play a vital role in drug-induced liver injury. Rutaecarpine has a secondary amine structure that may be activated to RMs. The aim of the study was to investigate the inhibition of rutaecarpine on CYPs and explore the possible relationship between RMs and potential hepatotoxicity. 3. A cell counting kit-8 cytotoxicity assay indicated that rutaecarpine can decrease the primary rat hepatocyte viability, increase lactate dehydrogenase and reactive oxygen species, reduce JC-1, and cause cell stress and membrane damage. The indexes were significantly restored by adding ABT, an inhibitor of CYPs. A cocktail assay showed that CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 can be inhibited by rutaecarpine in human liver microsomes. The IC50 values of CYP1A2 with and without NADPH were 2.2 and 7.4 µM, respectively, which presented a 3.3 shift. The results from a metabolic assay indicated that three mono-hydroxylated metabolites and two di-hydroxylated metabolites were identified and two GSH conjugates were also trapped. 4. Rutaecarpine can inhibit the activities of CYPs and exhibit a potential mechanism-based inhibition on CYP1A2. RMs may cause herb-drug interactions, providing important information for predicting drug-induced hepatotoxicity.
Subject(s)
Chemical and Drug Induced Liver Injury/enzymology , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Indole Alkaloids , Quinazolines , Animals , Chemical and Drug Induced Liver Injury/pathology , Cytochrome P-450 Enzyme Inhibitors/adverse effects , Cytochrome P-450 Enzyme Inhibitors/pharmacokinetics , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Humans , Indole Alkaloids/adverse effects , Indole Alkaloids/pharmacokinetics , Indole Alkaloids/pharmacology , Quinazolines/adverse effects , Quinazolines/pharmacokinetics , Quinazolines/pharmacology , RatsABSTRACT
1. Rhein, an active ingredient in the root of rhubarb, is used for its beneficial effects in a variety of clinical applications including the treatment of osteoarthritis and diabetic nephropathy. However, its hepatotoxicity has been reported in recent years. Rhein belongs to the conjugate structure which could be activated to reactive metabolites (RMs) inducing side-effects. This study is to explore the relationship between RMs and hepatotoxicity. 2. Based on the early detection of RMs, we have established a series of key technologies to research rhein hepatotoxicity mechanism: IC50 shift experiments and reduced glutathione (GSH) trapping experiment are adopted to identify RMs. The model of low activity of CYP450 enzymes (CYPs) in primary rat hepatocyte is constructed to analyze the relationship between the primary metabolic enzyme and hepatotoxicity of rhein better. 3. The IC50 shift value for CYP2C19 is 1.989, it suggests that CYP2C19 could activate rhein to RM. The structure of RM is epoxide intermediate. Besides, it is found that CYP2C19 is a primary metabolic enzyme for rhein. In the cytotoxicity assay, it is reported that rhein could cause mitochondrial dysfunction. Furthermore, mitochondrial membrane potential (Δψm) and AST levels could be restored by adding inhibitor of CYP2C19 together with rhein, which further shows that CYP2C19 could mediate the hepatotoxicity of rhein. 4. We put forward the possible mechanism that reactive metabolite activation by CYP2C19 mediated rhein hepatotoxicity, it provides important information on predicting in vivo drug-induced liver injury (DILI).
Subject(s)
Anthraquinones/toxicity , Cytochrome P-450 CYP2C19 Inhibitors/toxicity , Cytochrome P-450 CYP2C19/metabolism , Hepatocytes/drug effects , Reactive Oxygen Species/metabolism , Animals , Chemical and Drug Induced Liver Injury/pathology , Chromatography, Liquid , Drug Interactions , Glutathione/metabolism , Hepatocytes/metabolism , Inhibitory Concentration 50 , Male , Membrane Potential, Mitochondrial , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
We describe a new method of obtaining three-dimensional (3D) images of detached retina. Twelve-slice photos of the partial retina were obtained according to the twelve positions on a clock face. Twelve sections were then cut from these photos and joined together. Each sector was resized to match nearby sectors and the complete retinal picture was then created. A sphere mapping algorithm was used to map the two-dimensional (2D) picture to a sphere, which was then used to simulate the actual eyeball. Finally, a 3D image of the entire retina with a clearly visible detached section was created by the Visualization Toolkit (VTK).
