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21.
Lambert H.M. Janssen Anneloes L. van Til Frans B. van Duijneveldt 《Journal of electroanalytical chemistry (Lausanne, Switzerland)》1992,342(2):161-178
The reduction of the quinone moiety, which is found in many anti-cancer agents, is still a poorly understood process. It is commonly assumed that the reduction of a quinone by the uptake of two electrons and two protons leads to the active hydroquinone form. For a better understanding of these reactions electrochemical data, obtained for a series of substituted benzoquinones, were analyzed. In addition quantum chemical calculations on the STO-3G level were performed to obtain data for the one- and two-electron reduction.From the electrochemical experiments, thermodynamic data can be obtained which show that the unfavourable free energy of electron uptake is overcome by the favourable binding of protons. Both reactions are influenced by the electronic properties of the substituents, as demonstrated by Hammett-type relationships between the free energy of these reactions and the sigma-para character of these substituents. In these relationships the reaction constant of the electron uptake process has an absolute value which is five times higher than that of the proton uptake.Quantum chemical calculations yielded energy values for the one-electron uptake, as expressed by U(LUMO), and for the total reduction process. Most of the results from these calculations are in accord with the thermodynamic study. The calculations also revealed a conformational change to take place upon reduction of NH2 and N(CH2)2 substituted benzoquinones, which might be important for chemical and biological activity. 相似文献
22.
Over the last 7 years, under the Editorship of Kim Fox, theEuropean Heart Journal has becomean increasingly important internationalclinical journal in the field of cardiovascular medicine. This has been reflected in an increase in the official ISI impactfactor from 1.682 in 1995 to 相似文献
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Marko Korosec Ignac Zidar Dik Reits Craig Evinger Frans Vanderwerf 《Movement disorders》2006,21(8):1248-1251
We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks. 相似文献
25.
Femke M van de Water Johanna M Boleij Janny G P Peters Frans G M Russel Rosalinde Masereeuw 《European journal of pharmaceutical sciences》2007,30(1):36-44
The activity of P-glycoprotein (Pgp/MDR1/ABCB1) and multidrug resistance proteins (MRP/ABCC) influence the pharmacokinetics and bioavailability of many drugs. Few suitable cell lines for the study of drug transport exist. Additional non-human cell lines may help clarify species differences and contribute to the current knowledge of drug transport. The aim of the present study was to characterize three rat epithelial cell lines for transporter expression and activity. Transporter expression was assessed in intestinal IEC-6 and renal GERP and NRK-52E cells using RT-PCR and Western blot analysis. Pgp and Mrp transport activity were analyzed by measuring calcein accumulation and glutathione-S-bimane efflux, respectively. The three cell lines showed Pgp expression and Pgp-dependent transport, both decreasing with culture time after reaching confluency. Besides Pgp, cells expressed Mrp1, Mrp3, Mrp4, and Mrp5, while Mrp2 and Mrp6 were absent. In addition, they showed temperature- and Mrp-dependent efflux of glutathione-S-bimane. Exposure to a panel of different inhibitors showed that this efflux was probably mediated by Mrp4. In conclusion, the three rat epithelial cell lines investigated showed Pgp and Mrp expression and transport. Mrp dependent transport was most likely mediated by Mrp4. In future, these cell lines may be used as in vitro models to study drug transport. 相似文献
26.
Microvascular function in viable myocardium after chronic infarction does not influence fractional flow reserve measurements. 总被引:1,自引:0,他引:1
Koen M Marques Paul Knaapen Ronald Boellaard Adriaan A Lammertsma Nico Westerhof Frans C Visser 《Journal of nuclear medicine》2007,48(12):1987-1992
Fractional flow reserve (FFR) is an index of coronary stenosis severity. FFR is the ratio of hyperemic myocardial flow in the stenotic area to maximal flow in that same territory without stenosis and can be measured with a pressure wire. In patients with prior infarction, measuring FFR in infarct-related arteries may be different for 2 reasons: a smaller mass of viable myocardium depending on the stenotic infarct-related artery and greater microvascular resistance in the infarcted area than in the reference area. When microvascular resistance does not differ between the infarcted and the reference areas, FFR should equal relative flow reserve (RFR). RFR is the ratio of myocardial blood flow in the stenotic area to blood flow in a normally perfused reference area, at maximal hyperemia. H(2)(15)O PET measures myocardial flow within only the viable areas of an infarct and can be used to measure RFR. The present study assessed in patients with chronic myocardial infarction whether microvascular resistance in the infarct is different from that in the reference area. Therefore, the correlation between FFR and RFR using H(2)(15)O PET was studied. METHODS: In the catheterization laboratory, FFR was measured in the infarct-related artery and a reference coronary artery. The H(2)(15)O PET study and FFR measurements were performed on the same day in 22 patients. RESULTS: In 27 patients, the mean interval between the PET study and infarction was 3.3 y. Most patients had an anterior infarction, and the mean ejection fraction was 44%. The mean FFR and RFR values were 0.75 +/- 0.16 and 0.74 +/- 0.18, respectively. A significant correlation (r = 0.81; P < 0.0001) was found between FFR and RFR. The linear regression line was close to the line of identity. CONCLUSION: In patients with chronic myocardial infarction and a reduced ejection fraction, a good correlation was found between FFR measurements in the infarct-related artery and RFR. Because the linear regression line between FFR and RFR was close to the line of identity, one can conclude that microvascular resistance in the viable myocardium does not differ from that in the reference area. 相似文献
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L V Dekker P N De Graan H Spierenburg M De Wit D H Versteeg W H Gispen 《European journal of pharmacology》1990,188(2-3):113-122
Phosphorylation of the neuron-specific substrate of protein kinase C (PKC), B-50 (GAP-43), was studied parallel with noradrenaline release in rat brain synaptosomes. Both could be evoked by treating the synaptosomes with high K+ or veratridine. Phorbol 12,13-dibutyrate enhanced depolarization-induced B-50 phosphorylation and noradrenaline release. To investigate the involvement of PKC-mediated B-50 phosphorylation in noradrenaline release, we applied a variety of kinase inhibitors. Prior to measuring the effects of these inhibitors in intact synaptosomes, we determined their effectivity and specificity in a membrane phosphorylation assay. H-7 most specifically inhibited PKC-dependent phosphorylation, whereas calmidazolium inhibited calmodulin-dependent phosphorylation. Polymyxin B affected both protein kinase systems. Only polymyxin B effectively inhibited noradrenaline release in the intact synaptosomes. We conclude that PKC as well as calmodulin-dependent processes are important for the release event. Data are discussed in view of the presumed function of B-50 as a calmodulin-binding protein. 相似文献
29.
Auke J. S. Renard Ren P. H. Veth Maciej Pruszczynksi Jaap Hoogenhout Jos Bkkerink Frans J. M. Van Der Staak Theo Wobbes Josef A. M. Lemmens Ren van Hoesel Jim R. Van Horn 《Journal of surgical oncology》1995,60(4):250-256
This paper describes 29 patients with Ewing's sarcoma of bone treated between 1975 and 1990 at the University of Nijmegen Hospital, Nijmegen, The Netherlands. Osteomyelitis was the primary diagnosis in 24%. Treatment consisted of chemotherapy in combination with surgery and/or radiotherapy. Nine patients received radiotherapy only; five of them died of disease. Five patients underwent an intralesional excision; four of them died of disease. Twelve patients underwent a wide excision; there is no evidence of disease in any of them. Three patients underwent a radical disarticulation; all died of disease. The disease-free survival at 1.5 years was 66%. This figure at 5 years was 55%. After wide excision and reconstruction in tumors of expendable, femoral or radial bones good functional results were obtained in all cases. © 1995 Wiley-Liss, Inc. 相似文献
30.