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11.
Padmaja Yalamanchili Eric Wexler Megan Hayes Ming Yu Jody Bozek Mikhail Kagan Heike S. Radeke Michael Azure Ajay Purohit David S. Casebier Simon P. Robinson 《Journal of nuclear cardiology》2007,14(6):782-788
Background
BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention
mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02
was studied in vivo in mice.
Methods and Results
Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC50 of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC50 of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers
of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%)
and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC50 value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics
for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t1/2) uptake was very rapid (approximately 35 seconds), and washout t1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02
had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver
ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization
and demonstrated sustained myocardial uptake through 55 minutes.
Conclusions
F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake
and slow washout. These characteristics allow fast and sustained accumulation in the heart. 相似文献
12.
Claudia Trenkwalder MD Heike Benes MD Ludger Grote MD Svenja Happe MD Birgit Högl MD Johannes Mathis MD Gerda M. Saletu‐Zyhlarz MD Ralf Kohnen PhD CALDIR study group 《Movement disorders》2007,22(5):696-703
We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline. 相似文献
13.
Dr. med. Thorsten Schäfer Heike Vogelsang 《Somnologie - Schlafforschung und Schlafmedizin》2002,6(2):79-84
Summary Question of the study Nasal continuous positive airway pressure (CPAP) prevents collapse of the upper airway during sleep in patients with obstructive sleep apnea provided that a positive transmural pressure can be maintained during inspiration. We examined pressure-flow characteristics in seven CPAP and bilevel devices during spontaneous breathing.
Methods The CPAP devices were set to a pressure level of 9.8 hPa (10 cm H2 O) and adapted to a pneumotachograph using a standard CPAP hose and an outlet valve. We continuously measured flow, volume and pressure during resting ventilation and increasing voluntary hyperventilation and analysed the dependence of the variables on a breath-to-breath basis.
Results Mean CPAP pressures differed between the devices (9.9 – 10.6 hPa) despite the same settings. In all machines pressure fell during inspiration to 8.4 – 9.8 hPa and increased during expiration to 11.1 – 11.7 hPa. This effect increased with higher flow rates. Maximum expiratory pressures rose to 12 – 19 hPa at peak flow rates of 2 l/s, mean expiratory pressures to 9.5 – 16 hPa. Inspiratory pressures dropped to 8.5 – 4.5 hPa (minimum) and 10.5 – 6.0 (mean). Bilevel devices showed a higher stability than CPAP devices. Pressure swings during the respiratory cycle increased the additional work of breathing.
Conclusions Due to differences in mean and effective CPAP levels CPAP devices are not simply exchangeable but should be individually adapted. Patients with higher minute ventilation might benefit from more stable CPAP machines. The impact on patients' compliance remains to be evaluated. 相似文献
Methods The CPAP devices were set to a pressure level of 9.8 hPa (10 cm H
Results Mean CPAP pressures differed between the devices (9.9 – 10.6 hPa) despite the same settings. In all machines pressure fell during inspiration to 8.4 – 9.8 hPa and increased during expiration to 11.1 – 11.7 hPa. This effect increased with higher flow rates. Maximum expiratory pressures rose to 12 – 19 hPa at peak flow rates of 2 l/s, mean expiratory pressures to 9.5 – 16 hPa. Inspiratory pressures dropped to 8.5 – 4.5 hPa (minimum) and 10.5 – 6.0 (mean). Bilevel devices showed a higher stability than CPAP devices. Pressure swings during the respiratory cycle increased the additional work of breathing.
Conclusions Due to differences in mean and effective CPAP levels CPAP devices are not simply exchangeable but should be individually adapted. Patients with higher minute ventilation might benefit from more stable CPAP machines. The impact on patients' compliance remains to be evaluated. 相似文献
14.
Michael A Flierl Heike Schreiber Markus S Huber-Lang 《Journal of investigative surgery》2006,19(4):255-265
Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS. 相似文献
15.
Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. 总被引:21,自引:0,他引:21
Heike A Bischoff Hannes B St?helin Walter Dick Regula Akos Margrith Knecht Christian Salis Matthias Nebiker Robert Theiler Michael Pfeifer Bettina Begerow Robert A Lew Martin Conzelmann 《Journal of bone and mineral research》2003,18(2):343-351
Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function. 相似文献
16.
The transmission/disequilibrium test (TDT) is extended in two ways for a multiallelic marker: (1) to compare transmitted and nontransmitted alleles from a single heterozygous parent and (2) to compare genotypes formed by the two transmitted alleles and genotypes formed by the two nontransmitted alleles using the information on both parents, heterozygous or not, simultaneously. © 1995 Wiley-Liss, Inc. 相似文献
17.
S Sone H Yanagawa Y Nishioka E Orino G Bhaskaran A Nii K Mizuno Y Heike F Ogushi T Ogura 《The European respiratory journal》1992,5(2):174-181
The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha. 相似文献
18.
Heike Friedrich Bernd Fussnegger Karl Kolter Roland Bodmeier 《European journal of pharmaceutics and biopharmaceutics》2006,62(2):171-177
The dissolution rate of the model drugs carbamazepine and nifedipine was improved by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile solvents onto carriers with a large surface area. This was accomplished by dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2-pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil) or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil 200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil because of the smaller surface area. Differential scanning calorimetry measurements showed higher interactions between drugs and Kollidon compared to Aerosil, suggesting a low aggregation of precipitated drug particles. The drug release from the adsorbent systems was enhanced when compared to micronized drug and independent of the drug loading in the investigated range. The drugs were also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40-hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto Kollidon. These adsorbent systems also exhibited an increased dissolution rate when compared to pure drug. 相似文献
19.
20.
Eva-Maria Brick Heike Rudolph Jens Arnold Ralph G Luthardt 《Computerized medical imaging and graphics》2004,28(3):159-165
The three-dimensional (3D) evaluation and comparison of free-form-surfaces is a complex problem [Dent. Mater. 8 (1992) 49; J. Dent. Res. 76 (1997) 1799; Dent. Mater. 16 (2000) 145; J. Prosthet. Dent. 70 (1993) 457; Dent. Mater. 19 (2003) 19]. However, it is essential in order to analyze the sinter shrinkage of dental ceramic-restorations where isotropic and linear shrinkage is desired for accurate fit on the prepared teeth. In this article, we examine the 3D sinter shrinkage in general and for nine copings from alumina in particular. Using various scaled CAD-models in an iteration scheme, each model was compared to the filtered point cloud of the coping, determining the surface-cloud difference. The magnitude of deviations from linear sinter shrinkage was investigated. Furthermore, a new fabrication process for ceramic-restorations is introduced. 相似文献