Fully Automatic Scar Segmentation for Late Gadolinium Enhancement MRI Images in Left Ventricle with Myocardial Infarction.

Numerous methods have been published to segment the infarct tissue in the left ventricle, most of them either need manual work, post-processing, or suffer from poor reproducibility. We proposed an automatic segmentation method for segmenting the infarct tissue in left ventricle with myocardial infarction. Cardiac images of a total of 60 diseased hearts (55 human hearts and 5 porcine hearts) were used in this study. The epicardial and endocardial boundaries of the ventricles in every 2D slice of the cardiac magnetic resonance with late gadolinium enhancement images were manually segmented. The subsequent pipeline of infarct tissue segmentation is fully automatic. The segmentation results with the automatic algorithm proposed in this paper were compared to the consensus ground truth. The median of Dice overlap between our automatic method and the consensus ground truth is 0.79. We also compared the automatic method with the consensus ground truth using different image sources from different centers with different scan parameters and different scan machines. The results showed that the Dice overlap with the public dataset was 0.83, and the overall Dice overlap was 0.79. The results show that our method is robust with respect to different MRI image sources, which were scanned by different centers with different image collection parameters. The segmentation accuracy we obtained is comparable to or better than that of the conventional semi-automatic methods. Our segmentation method may be useful for processing large amount of dataset in clinic.

Polyamidomine dendrimers: an excellent drug carrier for improving the solubility and bioavailability of puerarin.

The potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers and oral drug delivery system was well known. Herein, we investigated the possibility of PAMAM dendrimers for promoting the solubility and oral bioavailability of puerarin. In the present study, the effect of PAMAM dendrimers with different generations (G1.5, G2, G2.5, and G3) on the solubility of puerarin was evaluated at different concentrations and pH conditions. Further more, the puerarin-G2 dendrimer complex was conducted for the in vitro hemolytic toxicity studies and pharmacokinetics studies in rats. The solubility of puerarin was significantly higher in the presence of the full generation dendrimers (e.g. G2 and G3). No significant hemolysis was observed on erythrocytes (G2, 0-2.5 mg/mL) in the hemolytic toxicity studies. The pharmacokinetics parameters Tmax, Cmax, and AUC0-8 h of puerarin suspension solution and puerarin-G2 dendrimer complex solution were 0.76 h, 1.50 µg/mL, 7.33 µg·h/mL and 0.33 h, 6.49 µg/mL, 14.02 µg·h/mL, respectively. These studies demonstrate that PAMAM dendrimers may be a promising strategy for peroral delivery of puerarin.

The absorption characteristics of bifendate solid dispersion in rat intestinal tissue.

AIM: Research on bifendate intestinal absorption. METHOD: The single passed intestinal backflow method was used. Bifendate with different concentrations, bifendate with and without 2,4-dinitrophenol, verapamil, and probenecid, and solid state of bifendate in different systems were studied. RESULT: Change of concentration and the presence of energy inhibitor, P-glycoprotein inhibitor and multidrug-resistant protein inhibitor did not affect the K(a) of bifendate intestinal absorption; there were obvious differences among intestinal absorption of native drug, solid dispersion, and physical mixtures. CONCLUSION: The result indicated that the intestinal absorption mechanism of bifendate is passive transport. Solid state of bifendate in different systems could affect the intestinal absorption.

[The effect of polyamidoamine (PAMAM) dendrimers on the solubility and pharmacokinetics of breviscapine].

To study the solubilization of breviscapine with polyamidoamine (PAMAM) dendrimers and probe the solubilizing mechanism and investigate the influence of PAMAM dendrimers on the pharmacokinetics of breviscapine, the solubilization of breviscapine by PAMAM dendrimers of generations G1, G1.5, G2 and G2.5 with different concentrations were determined and compared in different pH conditions. Twelve rats randomized into 2 groups were separately orally administered breviscapine and breviscapine combining with PAMAM. Drug in plasma was extracted and determined with HPLC. In pH condition lower than 7.0, the solubilization of breviscapine by PAMAM dendrimers enhanced as the generation and concentration of PAMAM dendrimers as well as the pH increased. Its solubilizing mechanism involves an electrostatic interaction between the carboxyl group of breviscapine and the primary amines and tertiary amines of PAMAM dendrimers. The pharmacokinetics parameters Cmax and AUC0-8 h of breviscapine were (119.65 +/- 9.36) ng x mL(-1) and (370.09 +/- 63.08) ng x h x mL(-1). For breviscapine combined with PAMAM dendrimers, the Cmax and AUC0-8 h were (518.17 +/- 17.07) ng x mL(-1) and (1,219.47 +/- 201.87) ng x h x mL(-1), respectively. There were significant differences of AUC0-8 h between breviscapine and breviscapine combined with PAMAM dendrimers (P < 0.01). PAMAM dendrimers can greatly increase the solubility of breviscapine in water and can improve the oral bioavailability of breviscapine significantly.

[Effects of the liposomes coated by chitosan and its derivatives on the gastrointestinal transit of insulin].

AIM: To study the effect of the liposomes coated by chitosan and its derivatives as oral dosage form for peptide drugs on the gastrointestinal (GI) transit of drugs. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. The in situ perfusion experiment was used to investigate the enteral absorption of insulin. The hypoglycemic effects of insulin were investigated using the glucose oxidase method after administration in rats. The insulin concentrations of serum and enteral tissues were determined by radio-immunoassay in rats. RESULTS: In in situ local intestinal perfusion experiment, the duodenum was the best segment for the absorption of the insulin liposomes coated by chitosan (CH) or chitosan-EDTA conjugates (CEC) , and double-coated by CH-CEC; the colon was the best segment for the absorption of the insulin solution from rat intestine; but the best segment for the absorption of the uncoated and N-trimethyl chitosan chloride (TMC) coated insulin liposomes was unclear. In all segments, the enteral absorption of the insulin liposomes double-coated by CH-CEC was superior to that of other insulin liposomes. CONCLUSION: The insulin-liposomes coated by chitosan and its derivatives can enhance enteral absorption of insulin and increase stability of insulin in GI tract.

Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice.

AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS: In all the insulin liposomes, the insulin liposomes coated by 0.2% chitosan (Mr 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%+/-6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice. CONCLUSION: Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.

[Studies on the insulin-liposomes double-coated by chitosan and chitosan-EDTA conjugates].

AIM: To evaluate the characteristics, the hypoglycemic efficacy and the pharmacokinetics of the insulin-liposomes double-coated by chitosan (CH) and chitosan-EDTA conjugates (CEC). METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. The protection of insulin against peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of insulin-liposomes were investigated using the glucose oxidase method after oral administration to rats. Serum insulin concentration in rats were determined by radio-immunoassay, and were assessed by Pkanalyst computer program. RESULTS: The insulin-liposomes double-coated by CH and CEC was shown to protect insulin against digestion of pepsin, trypsin and gastrointestinal contents. In glucose tolerance test in normal rats, as compared with phosphate buffer solution control group, the insulin-liposomes coated by CH and CEC could reduce the glucose-induced peak of hyperglycemia. The reduction of the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes. When administered intragastrically to normal rats, the insulin-liposomes coated by CH and CEC could reduce glycemia measured after an overnight fast. The hypoglycemic effect the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes, and the dosage of 50 mu x kg(-1) decreased by 45.98% of initial blood glucose level at 1 h. As compared with subcutaneous injection, the relative pharmacological bioavailability was 17.02% calculated by area under the curve of glucose level versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. The serum insulin concentration-time curves were found to best fit the one-compartment open model. As compared with subcutaneous injection, the relative bioavailability was 8.91% calculated by the area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. CONCLUSION: The stability and absorption of insulin-liposomes double-coated by CH and CEC was superior to that of the insulin-liposomes coated either by CH, or by CEC respectively.

[Characterization of CD10 expression and its significance in minimal residual disease detection in childhood B-acute lymphoblastic leukemia].

To observe the expressions of CD10 in childhood B-acute lymphoblastic leukemia (B-ALL) and to define the role of CD10 in minimal residual disease (MRD) detection. 58 cases of childhood B-ALL were studied in this program. Four-color flow cytometry was used to analyze the characteristics of B-ALL phenotypes. The four-color fluorochrome labeled antibody combinations of CD10 with other markers were used to detect MRD. The results showed that CD10 overexpression (CD10(bright)) was detected in 65.5% (38/58) of B-ALL patients and a strong correlation between CD10(bright) and CD34 expression was also observed, i.e. CD10(bright) expression most frequently happened in B-ALL with high percentage of CD34 positive cells. In detection of MRD, CD10(bright), combined with other markers, could effectively distinguish normal cells with leukemic cells, even if there was no any other marker that can be used. It is concluded that CD10(bright) expression correlates with high expression of CD34 in B-ALL, it is a good marker for MRD detection. The combination of CD10 and other markers can be applied in B-ALL MRD detection with flow cytometry.

[Detection of minimal residual disease in childhood B-ALL by flow cytometry].

OBJECTIVE: To establish a flow cytometric method for detecting minimal residual disease (MRD) in children with B-ALL and evaluate its clinical application. METHODS: Fifty-eight childhood B-ALL cases entered this study and 30 MRD analyses were performed after remission induction therapy. Four-color fluorochrome labeled monoclonal antibodies were used to analyze the cell immunophenotypes. Cells from normal bone marrow were used as controls. The leukemic cell populations located in flow cytometry dot plots different from those of normal were considered to be the markers of interest in the first step screening, and then used to monitor MRD step after therapy. RESULTS: Fifty-eight cases of childhood B-ALL were screened for antibodies combinations of interest and were identified in 89.7% (52/58) of these cases. The four-color antibody combinations consisted of CD(10)/CD(34)/CD(19) plus another effective marker such as CD(38), CD(65), CD(66c), CD(21). The sensitivity of this method was 0.01%, much higher than microscopic inspection. In 8 cases whose bone marrow microscopically showed no residual leukemic cells, the percentage of leukemic cells were identified with this method of 0.028%, 1.430%, 3.050%, 0.015%, 5.660%, 2.700%, 0.027%, and 0.069%, respectively. CONCLUSION: The application of flow cytometry in MRD monitoring can significantly improve the detection sensitivity in childhood B-ALL, thus facilitate the further treatment decision and follow-up.

[Hypoglycemic effect of polysaccharide-coated insulin liposomes after oral administration in mice].

AIM: To evaluate the hypoglycemic effect of chitosan-coated and sodium alginate-coated insulin liposomes after oral administration in mice. METHODS: Insulin-liposomes were prepared by reverse-phase evaporation. Chitosan and alginate coating was carried out by mixing liposomal suspension with chitosan and sodium alginate solutions, followed by incubation. The particle size and morphology of insulin-liposomes were determined using laser light scattering instrument and transmission electron microscopy (TEM). The entrapment efficiency was analyzed using HPLC and ultracentrifuge. The protection of insulin from peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of polysaccharide-coated insulin liposomes were investigated using the glucose oxidase method after oral administration in mice. RESULTS: The particle size of uncoated, chitosan-coated and alginate-coated insulin-liposomes was (138 +/- 31) nm, (230 +/- 20) nm and (266 +/- 19) nm, respectively. All insulin-liposomes were of spherical or ellipsoidal shape. The entrapment efficiencies were 81.6%, 73.5% and 68.7%, respectively. Insulin was protected from tryptic digestion by chitosan-coated liposomes and protected from peptic digestion by alginate-coated liposomes. The hypoglycemic effects of insulin-liposomes, coated with 0.1% chitosan and 0.1% sodium alginate, were observed. CONCLUSION: Chitosan-coated and sodium alginate-coated liposomes were shown to reduce peptic or tryptic digestion on insulin, and enhance enteral absorption of insulin.