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1.
Riemer H J A Slart Ali Agool Dirk J van Veldhuisen Rudi A Dierckx Jeroen J Bax 《Journal of nuclear medicine》2006,47(8):1307-1311
SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. RESULTS: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability. 相似文献
2.
PLASMA FOLLISTATIN CONCENTRATIONS INCREASE FOLLOWING LIPOPOLYSACCHARIDE ADMINISTRATION IN SHEEP 总被引:1,自引:0,他引:1
Rudi Klein Iain J. Clarke† Mark P. Hedger† David M. Robertson† 《Clinical and experimental pharmacology & physiology》1996,23(8):754-755
1. The effect of inflammation induced by lipopolysaccharide (LPS) injection on plasma follistatin (FS) concentrations was investigated. 2. Plasma FS and tumour necrosis factor-α concentrations increase following LPS administration in ewes. 3. The rise in FS is similar, but more sustained, to that previously observed after surgery. 4. These results indicate a possible functional link between FS, inflammation and the acute-phase response. 相似文献
3.
4.
Alexander Mülsch Eberhard Bassenge Rudi Busse 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):767-770
Summary Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase coincubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 + 0.5-fold (from 31 + 9 to 153 + 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 + 15% (with 2 M free calcium; EC50 0.3 M). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 M) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation NG-nitro-L-arginine (1 mM) and by LY 83583 (1 M), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells.
Send of fprint requests to A. Mülsch, at the above address 相似文献
5.
Shinkai T De Luca V Zai G Shaikh S Matsumoto C Arnold PD Hwang R King N Trakalo J Potapova N Wong G Hori H Wong AH Ohmori O Nakamura J Kennedy JL 《Psychiatric genetics》2004,14(3):177-180
OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia. 相似文献
6.
Variation of the photoactivation rate across radiation fields of three different bremsstrahlung beams of two medical accelerators has been measured, making use of the photonuclear reactions in natural indium probes: 115In(y,y')115mIn and 115In(y,n)114mIn. The third nuclear reaction, 115In(n,y)116mIn, was used to detect the presence of neutrons in the photon beam and to estimate the spatial distribution of thermal and fast neutrons in the patient plane as a function of collimator opening. 相似文献
7.
Adenoviral vectors expressing siRNAs for discovery and validation of gene function 总被引:5,自引:0,他引:5
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Arts GJ Langemeijer E Tissingh R Ma L Pavliska H Dokic K Dooijes R Mesić E Clasen R Michiels F van der Schueren J Lambrecht M Herman S Brys R Thys K Hoffmann M Tomme P van Es H 《Genome research》2003,13(10):2325-2332
RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts. 相似文献
8.
Daniel Lamontagne Ulrich Pohl Rudi Busse 《Pflügers Archiv : European journal of physiology》1991,418(3):266-270
The effects of a recently described inhibitor of endothelial NO synthesis, N
G-nitro-l-arginine (l-NNA), on the vasomotor responses to endothelium-dependent and independent vasodilators, and on the release of endothelium-derived relaxing factor (EDRF), were studied in the isolated saline-perfused rabbit heart. Infusion of l-NNA (30 M) resulted in a 52±12% increase in basal coronary perfusion pressure. The vasomotor responses to 1 M acetylcholine (ACh) and serotonin after l-NNA became biphasic, showing a small transient dilation followed by a pronounced vasoconstriction. In contrast, the dilation observed with sodium nitroprusside was not affected by l-NNA. None of the above-mentioned effects was elicited by the Stereo-isomer d-NNA. Similarly, an increase in the basal coronary perfusion pressure by endothelin-1 (0.3 nM) to the same level as observed with l-NNA did not alter the vasomotor responses to ACh and sodium nitroprusside. The increase in cyclic GMP (cGMP) in platelets passing through the coronary vascular bed was used as an index of EDRF release. Platelet cGMP amounted to 0.50±0.10 pmol/mg protein after passage through the coronary bed of the unstimulated heart. When platelets were injected during an ACh infusion (1 M), a 2.7 fold increase in cGMP was observed (P<0.01). After a 30-min infusion with l-NNA, the cGMP content of platelets passing through the unstimulated heart was reduced by 62%. Likewise, the ACh-induced increase in platelet cGMP was totally blocked. These results show that l-NNA inhibits EDRF release, and is thus a potent and selective inhibitor of EDRF-mediated dilation in the isolated rabbit heart. 相似文献
9.
Brosens I Gordts S Valkenburg M Puttemans P Campo R Gordts S 《Human reproduction (Oxford, England)》2004,19(8):1689-1692
While the appropriate method for the investigation of female infertility continues to be debated, the timing of the investigation has received less attention. The current approach is time-consuming, and paradoxically may lead to overtreatment as well as undertreatment. Recent findings on fecundity and the conception window in humans have important implications for the timing of the investigation of female infertility. The findings support the view that fertility-oriented intercourse may have a major impact in reducing the time to pregnancy. Procedures for the investigation of female infertility are becoming less invasive and more accurate, while the therapies for infertility are more effective. It is proposed that under appropriate circumstances female infertility should be investigated after 6 months of fertility-oriented intercourse. 相似文献
10.
Nilius B Weidema F Prenen J Hoenderop JG Vennekens R Hoefs S Droogmans G Bindels RJ 《Pflügers Archiv : European journal of physiology》2003,445(5):584-588
The family of epithelial Ca(2+) channels (ECaC) is a unique group of highly Ca(2+)-selective channels consisting of two members, ECaC1 and ECaC2. We used carboxyl terminal truncations and mutants to delineate the molecular determinants of the Ca(2+)-dependent inhibition of ECaC. To this end, rabbit ECaC1 was expressed heterologously with green fluorescent protein (GFP) in human embryonic kidney 293 (HEK293) cells using a bicistronic vector. Deletion of the last 30 amino acids of the carboxyl terminus of ECaC1 (G701X) decreased the Ca(2+) sensitivity significantly. Another critical sequence for Ca(2+)-dependent inactivation of ECaC1 was found upstream in the carboxyl terminus. Analysis of truncations at amino acid 635, 639, 646, 649 and 653 disclosed a critical sequence involved in Ca(2+)-dependent inactivation at positions 650-653. C653X showed decreased Ca(2+) sensitivity, comparable to G701X, while E649X lacked Ca(2+)-dependent inactivation. Interestingly, the number of green fluorescent cells, which is an index of the number of transfected cells, was significantly smaller for cells transfected with truncations shorter than E649 than for cells transfected with wild-type ECaC. However, the expression level of GFP was restored in the presence of the ECaC blocker ruthenium red, suggesting that these truncations resulted in deleterious Ca(2+) influx. In conclusion, we have identified two domains in the carboxyl terminus of ECaC1 that control Ca(2+)-dependent inactivation. 相似文献