ABSTRACT
BACKGROUND: Three-dimensional magnetic field positioning and three-dimensional electric field positioning are two main technologies used in heart ablation, but their required equipments are very expensive. OBJECTIVE: To develop a new method of ablation catheter positioning by combining ultrasonic probe with ablation catheter. METHODS: Three-dimensional data of human heart were obtained from the anatomical data set of the body, and then a three-dimensional vector model of the endocardial surface was established. The basic parameters and scanning strategy of ultrasonic probe were designed and calculated, to compile a corresponding simulation software. Based on the three-dimensional endocardial vector model, the detection data of the ultrasonic probe were obtained by simulation calculation and processed. Then, the target surface characteristics were reconstructed, matching with the surface features of the proposed vector model. The position of the probe was finally determined. RESULTS AND CONCLUSION: The three-dimensional model of the endocardium was established based on the anatomical data set, and the ultrasonic surface detection data were obtained by the simulated ultrasonic irradiation. The reconstructed surface model with high accuracy exhibited a desired match with the target area in the three-dimensional model of endocardium. The error of the probe position and its theoretical position fulfilled the requirement of positioning accuracy. In conclusion, the use of ultrasonic imaging technology can accurately position the catheter probe in the heart during heart ablation, providing an accurate and reliable navigation for the implementation of heart ablation.
ABSTRACT
This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimer's disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.
Subject(s)
Animals , Female , Male , Mice , Rats , Blood-Brain Barrier , Metabolism , Brain , Metabolism , Cell Nucleus , Metabolism , Cerebral Cortex , Metabolism , Fibroblast Growth Factor 1 , Pharmacokinetics , Gene Products, tat , Pharmacokinetics , Hippocampus , Metabolism , Injections, Intravenous , Rats, Sprague-Dawley , Recombinant Fusion Proteins , PharmacokineticsABSTRACT
<p><b>AIM</b>To compare the effects of the non-mitogenetic human acidic fibroblast growth factor (nmhaFGF) and the human acidic fibroblast growth factor (haFGF) on the proliferation and MAPK signal transduction pathway of the malignant tumor cell and to study the clinical safety of nmhaFGF.</p><p><b>METHODS</b>The mammary tumor cells (MCF-7) were treated with haFGF and nmhaFGF separately. The mitogenic activities of both haFGF and nmhaFGF were detected by MTT method and the cell cycle was analyzed by flow cytometer (FCM). The expression levels of the signal proteins, Grb2 (growth factor receptor bound 2) and ERK1/2 (extracellular signal-regulated kinase 1/2), were detected by semi-quantitative Western blotting method.</p><p><b>RESULTS</b>The mitogenic activity of nmhaFGF was obviously lower than that of haFGF. The activity of nmhaFGF was weaker than that of the haFGF. The ratio of G1/G0, G2/M of haFGF was markedly lower than that of nmhaFGF and control group, and was reverse in S phase. The expression levels of both Grb2 and ERK1/2 of the nmhaFGF treated group were lower than that of the haFGF treated group and approaching the control group.</p><p><b>CONCLUSION</b>The mitogenic activity of the nmhaFGF decreased remarkably. Its mechanism probably via down-regulation of the expression of the signal moleculars, MAPK-ERK1/2 and Grb2.</p>
Subject(s)
Female , Humans , Breast Neoplasms , Metabolism , Pathology , Cell Cycle , Cell Line, Tumor , Down-Regulation , Fibroblast Growth Factor 1 , Genetics , Pharmacology , GRB2 Adaptor Protein , Metabolism , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Mitosis , MutationABSTRACT
In order to decrease the potential side-effects of human basic fibroblast growth factor (hbFGF) caused by its broadspectrum mitogenic activity, a single residue of hbFGF, the residue serine 108, was replaced with neutral alanine residue to construct a mutant of hbFGF (mhbFGF) with reduced mitogenic activity. The mutant was overexpressed in Escherichia coli BL21(DE3) by IPTG induction. The expression level of mhbFGF was about 30% of the total cellular protein. The expressed mhbFGF was purified by ionic exchange and heparin affinity chromatography from the supernatant of bacteria lysate. Measured by MTT method, the effect of mhbFGF on Balb/c 3T3 cell proliferation was much lower than that of wild-type hbFGF. The purified recombinant mhbFGF was prepared and sufficient for the following pharmacological and safety studies.
ABSTRACT
In order to decrease the potential side-effects of human basic fibroblast growth factor (hbFGF) caused by its broadspectrum mitogenic activity, a single residue of hbFGF, the residue serine 108, was replaced with neutral alanine residue to construct a mutant of hbFGF (mhbFGF) with reduced mitogenic activity. The mutant was overexpressed in Escherichia coli BL21(DE3) by IPTG induction. The expression level of mhbFGF was about 30% of the total cellular protein. The expressed mhbFGF was purified by ionic exchange and heparin affinity chromatography from the supernatant of bacteria lysate. Measured by MTT method, the effect of mhbFGF on Balb/c 3T3 cell proliferation was much lower than that of wild-type hbFGF. The purified recombinant mhbFGF was prepared and sufficient for the following pharmacological and safety studies.