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Jonson SD Bonasera TA Dehdashti F Cristel ME Katzenellenbogen JA Welch MJ 《Nuclear medicine and biology》1999,26(1):123-130
16beta-[18F]Fluoromoxestrol ([18]betaFMOX) is an analog of 16alpha-[18F]fluoroestradiol-17beta ([18F]FES), a radiopharmaceutical known to be an effective positron emission tomography (PET) imaging agent for estrogen receptor-positive (ER+) human breast tumors. Based on comparisons of target tissue uptake efficiency and selectivity in a rat model, [18F]betaFMOX was predicted to be as effective an imaging agent as [18F]FES. However, in a preliminary PET imaging study with [18F]FMOX of 12 patients, 3 of whom had ER+ breast cancer, no tumor localization of [18F]betaFMOX was observed. In search for an explanation for the unsuccessful [18F]betaFMOX clinical trial, we have examined the rate of metabolism of [18F]FMOX and [18F]FES in isolated rat, baboon, and human hepatocytes. We have also studied the effect of the serum protein sex hormone-binding globulin (SHBG), which binds [18F]FES better than [18F]betaFMOX, on these rates of metabolism. Immature rat hepatocytes were found to metabolize [18F]FES 31 times faster than [18F]betaFMOX, whereas mature rat cells metabolized [18F]FES only 3 times faster, and baboon and human hepatocytes only 2 times faster than [18F]betaFMOX. In the presence of SHBG, the metabolic consumption rate for [18F]FES in mature rat hepatocytes decreased by 26%. Thus, the very favorable target tissue uptake characteristics of [18F]betaFMOX determined in the rat probably result from its comparative resistance to metabolism (vis-a-vis [18F]FES) in this species, an advantage that is strongly reflected in comparative metabolism rates in rat hepatocytes. In the baboon and human, [18F]FES is extensively protein bound and protected from metabolism, an effect that may be reflected to a degree as a decrease in the rate of metabolism of this compound in baboon and human hepatocytes relative to [18F]betaFMOX. Thus in primates, SHBG may potentiate the ER-mediated uptake of [18F]FES in ER+ tumors by selectively protecting this ligand from metabolism and ensuring its delivery to receptor-containing cells. In addition to current screening methods for 18F-estrogens that involve evaluating in vivo ER-mediated uptake in the immature female rat, studies comparing the metabolism of the new receptor ligands in isolated hepatocytes, especially those from primates or humans, may assist in predicting the potential of these ligands for human PET imaging. 相似文献
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Arthur E. Schwartz Farrokh R. Maneksha W. Walter Backus Marc S. Kanchuger William L. Young 《Journal canadien d'anesthésie》1991,38(2):239-242
Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine. 相似文献
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Vincent L Soria C Mirshahi F Opolon P Mishal Z Vannier JP Soria J Hong L 《Arteriosclerosis, thrombosis, and vascular biology》2002,22(4):623-629
Cerivastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It inhibits the biosynthesis of cholesterol and its precursors: farnesyl pyrophosphate and geranylgeranyl pyrophosphate (GGPP), which are involved in Ras and RhoA cell signaling, respectively. Statins induce greater protection against vascular risk than that expected by cholesterol reduction. Therefore, cerivastatin could protect plaque against rupture, an important cause of ischemic events. In this study, the effect of cerivastatin was tested on angiogenesis because it participates in plaque progression and plaque destabilization. Cerivastatin inhibits in vitro the microvascular endothelial cell proliferation induced by growth factors, whereas it has no effect on unstimulated cells. This growth arrest occurs at the G(1)/S phase and is related to the increase of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). These effects are reversed by GGPP, suggesting that the inhibitory effect of cerivastatin is related to RhoA inactivation. This mechanism was confirmed by RhoA delocalization from cell membrane to cytoplasm and actin fiber depolymerization, which are also prevented by GGPP. It was also shown that RhoA-dependent inhibition of cell proliferation is mediated by the inhibition of focal adhesion kinase and Akt activations. Moreover, cerivastatin inhibits in vivo angiogenesis in matrigel and chick chorioallantoic membrane models. These results demonstrate the antiangiogenic activity of statins and suggest that it may contribute to their therapeutic benefits in the progression and acute manifestations of atherosclerosis. 相似文献
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Vahid Khori Ali Mohammad Alizadeh Zohre Gheisary Sadaf Farsinejad Farrokh Najafi Solmaz Khalighfard Fatemeh Ghafari Maryam Hadji Hamid Khodayari 《Lasers in medical science》2016,31(9):1775-1782
Low-level laser therapy (LLLT) is a form of photon therapy which can be a non-invasive therapeutic procedure in cancer therapy using low-intensity light in the range of 450–800 nm. One of the main functional features of laser therapy is the photobiostimulation effects of low-level lasers on various biological systems including altering DNA synthesis and modifying gene expression, and stopping cellular proliferation. This study investigated the effects of LLLT on mice mammary tumor and the expression of Let-7a, miR155, miR21, miR125, and miR376b in the plasma and tumor samples. Sixteen mice were equally divided into four groups including control, and blue, green, and red lasers at wavelengths of 405, 532, and 632 nm, respectively. Weber Medical Applied Laser irradiation was carried out with a low power of 1–3 mW and a series of 10 treatments at three times a week after tumor establishment. Tumor volume was weekly measured by a digital vernier caliper, and qRT-PCR assays were performed to accomplish the study. Depending on the number of groups and the p value of the Kolmogorov-Smirnov test of normality, a t test, a one-way ANOVA, or a non-parametric test was used for data analyses, and p?<?0.05 was considered to be statistically significant. The average tumor volume was significantly less in the treated blue group than the control group on at days 21, 28, and 35 after cancerous cell injection. Our data also showed an increase of Let-7a and miR125a expression and a decrease of miR155, miR21, and miR376b expression after LLLT with the blue laser both the plasma and tumor samples compared to other groups. It seems that the non-invasive nature of laser bio-stimulation can make LLLT an attractive alternative therapeutic tool. 相似文献
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Fatemeh Mohammadsaleh Maryam Dehdashti Jahromi Abdol Reza Hajipour Seyed Mostafa Hosseini Khodabakhsh Niknam 《RSC advances》2021,11(34):20812
1,2,3-Triazole is an interesting N-heterocyclic framework which can act as both a hydrogen bond donor and metal chelator. In the present study, C–H hydrogen bonding of the 1,2,3-triazole ring was surveyed theoretically and the results showed a good agreement with the experimental observations. The click-modified magnetic nanocatalyst Pd@click-Fe3O4/chitosan was successfully prepared, in which the triazole moiety plays a dual role as both a strong linker and an excellent ligand and immobilizes the palladium species in the catalyst matrix. This nanostructure was well characterized and found to be an efficient catalyst for the CO gas-free formylation of aryl halides using formic acid (HCOOH) as the most convenient, inexpensive and environmentally friendly CO source. Here, the aryl halides are selectively converted to the corresponding aromatic aldehydes under mild reaction conditions and low Pd loading. The activity of this catalyst was also excellent in the Suzuki cross-coupling reaction of various aryl halides with phenylboronic acids in EtOH/H2O (1 : 1) at room temperature. In addition, this catalyst was stable in the reaction media and could be magnetically separated and recovered several times.The C–H hydrogen bonding of a 1,2,3-triazole framework was studied. An Fe3O4–chitosan core–shell incorporating a triazole/Pd complex was investigated as a nanocatalyst in carbonylation and C–C coupling. 相似文献
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Yusof Ganji Farrokh Janabi-Sharifi Asim N. Cheema 《International journal of computer assisted radiology and surgery》2009,4(4):307-315
Objective Manual navigation of intracardiac steerable catheters is inaccurate, requires dexterity for efficient manipulation of the
catheter, and exposes the interventionalist to ionizing radiation. The objective of this research is to develop a system that
replaces the interventionalists’s hands in catheter manipulation for accurate and semi-automatic tele-navigation of catheters.
Methods Based on a proposed kinematic model for the distal shaft of the catheter, a system has been developed for assisted navigation
of intracardiac catheters. When the distal shaft of the catheter lies inside a cardiac chamber, a robotic apparatus is utilized
for automatic steering of the catheter tip to reach designated targets within the chamber.
Results The catheter modeling was validated through the experiments on three swine. The robotic system could navigate the catheter
tip to designated targets with a mean distance of 6.53 mm from the target.
Conclusion Preliminary in vivo studies demonstrate the feasible application of the system in catheter navigation and the validity of
catheter modeling and control strategies. 相似文献