Heterogeneity of cardiac sympathetic nerve activity and systolic dysfunction in patients with hypertrophic cardiomyopathy

金沢大学大学院医学系研究科Cardiac sympathetic nerve activity is changed in patients with hypertrophic cardiomyopathy (HCM). However, the relationship between heterogeneity of this activity and systolic left ventricular dysfunction in patients with HCM is not well established. This study was performed to evaluate the sympathetic nerve activity in various cardiac regions and to investigate the relationship between cardiac dysfunction and heterogeneity of the cardiac sympathetic nerve activity in patients with HCM. Methods: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM and 10 control subjects using planar imaging and SPECT by 123l-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar 123I-MIBG imaging, the heart-to-mediastinum activity ratios (H/M), at early (20 min) and delayed (3 h) acquisition, and the washout rate were calculated. Polar maps of the left ventricular myocardium were divided into 20 segments, and the dispersion (maximal to minimal values) and SD of uptake and the washout rate in 20 segments were calculated. Results: The early H/M did not differ between the 2 groups. The delayed H/M was significantly lower and the washout rate of the whole heart was significantly higher in the HCM group than those in the control group. In patients with HCM, the delayed H/M, early uptake dispersion, and SD of early uptake showed good correlation with the left ventricular end-diastolic and end-systolic dimensions and the percentage of fractional shortening. A stepwise regression analysis revealed that the SD of early uptake was a powerful determinant for the percentage of fractional shortening in patients with HCM. Conclusion: These results suggest that the heterogeneity of regional cardiac sympathetic nerve activity may be correlated with cardiac dysfunction in patients with HCM

Changes in cardiac sympathetic nerve innervation and activity in pathophysiologic transition from typical to end-stage hypertrophic cardiomyopathy

金沢大学大学院医学系研究科Left ventricular (LV) systolic function in hypertrophic cardiomyopathy (HCM) is usually normal. Late in the disease, however, LV systolic dysfunction and dilatation are recognized. Although abnormalities in cardiac sympathetic nerve activity in patients with HCM have been demonstrated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, the changes of cardiac sympathetic nerve activity throughout the clinical course from typical to end-stage HCM are unclear. The objective of this study was to evaluate the relationship between abnormalities on 123I-MIBG myocardial scintigraphy and pathophysiologic changes in patients with HCM. Methods: We performed 123I-MIBG scintigraphy on 46 patients with HCM and 18 age-matched control subjects. The patients were categorized into 3 groups: 28 patients with normal LV systolic function (group A), 9 patients with LV systolic dysfunction (group B), and 9 patients with LV systolic dysfunction and dilatation (group C). With planar 123I-MIBG imaging, the heart-to-mediastinum ratio for early and delayed acquisitions and the washout rate were calculated. With SPECT, polar maps of the LV myocardium were divided into 20 segments. The regional uptake and washout rate were calculated from semiquantitative 20-segment bull\u27s-eye analysis. Results: The early uptake was significantly lower in group C than in the control group (P < 0.01). The washout rate was progressively higher in group A, group B, and group C (P < 0.01). Reduced regional early uptake was found in 2.9 ± 3.4 (group A), 4.1 ± 4.7 (group B), and 7.4 ± 4.3 (group C) segments, respectively. In group C, regional early uptake was significantly reduced, predominantly in the interventricular septal wall, and regional washout rate was increased in the apex and lateral wall. Conclusion: These results suggest that cardiac sympathetic nerve abnormalities in patients with HCM may advance with development of LV systolic dysfunction and dilatation and that 123I-MIBG myocardial scintigraphy may be a useful tool for the evaluation of pathophysiologic changes in HCM

A novel method for measuring human hepatic lipase activity in postheparin plasma

金沢大学医薬保健研究域医学系The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylenenonylphenylether, 3 mM ATP, 3 mM MgCl2, 1.5 mM CaCl2, monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 μl of R-1 was incubated at 37°C with 3 μl of samples for 5 min, and 80 μl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P , 0.0001) than those in the conventional method using [ 14C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc

Normal values for nuclear cardiology: Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function

Myocardial normal databases for stress myocardial perfusion study have been created by the Japanese Society of Nuclear Medicine Working Group. The databases comprised gender-, camera rotation range- and radiopharmaceutical-specific data-sets from multiple institutions, and normal database files were created for installation in common nuclear cardiology software. Based on the electrocardiography-gated single-photon emission computed tomography (SPECT), left ventricular function, including ventricular volumes, systolic and diastolic functions and systolic wall thickening were also analyzed. Normal databases for fatty acid imaging using 123I-beta-methyl-iodophenyl-pentadecanoic acid and sympathetic imaging using 123I-meta-iodobenzylguanidine were also examined. This review provides lists and overviews of normal values for myocardial SPECT and ventricular function in a Japanese population. The population-specific approach is a key factor for proper diagnostic and prognostic evaluation

Increase of one-to-one particle encapsulation yield using dielectrophoretic alignment technique with boxcar-type electrodes (Translated)

We developed a technique which can increase the yield of one-to-one particle encapsulation by applying the dielectrophoretic particle alignment technique using boxcar-type electrodes. Dielectrophoretic force generated by the boxcar-type electrodes accelerate and decelerate the particles periodically as they flow in the electrode region. Further, the dielectrophoretic force is turned on and off at constant frequency. The force exerted on the particle periodically over space and time can align them in the streamwise direction with even interval. In this study, the boxcar-type electrodes were installed in the microchannel in the region upstream of the flow-focusing channel in which the water-in-oil droplets were generated. By adjusting the on-off period of the applied voltage generating the dielectrophoretic force to the period of the droplet generation, each particle could be separately encapsulated in the droplets. The principle of particle alignment using periodic force was first described based on a one-dimensional model. The flow structure and the characteristics of the droplet generation in the flow-focusing channel was then discussed in relation to the surface tension of the fluids and the wettability of the wall. We measured the velocity distribution of the particles flowing in the boxcar-type electrode region to evaluate the effects of the droplet generation on the motion of the particles and the alignment performance. The results showed that the particle could be aligned in the fluctuating flow caused by the droplet generation, and each particle can be encapsulated in different droplets. This was further demonstrated by measuring the probability function of the droplets containing specific number of particles, which showed that 100% yield of one-to-one particle encapsulation can be achieved under the investigated condition of particle number density of 0.4. Moreover, the throughput increased 46% compared to the case of having the particles supplied randomly

Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

Recent studies have shown that adipose-derived stromal/stem cells (ASCs) contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs). This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2) and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta). NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives