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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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Juraj Sprung MD PhD David Distel CRNA Jeffrey Grass MD Eric L. Bloomfield MD Ian C. Lavery MD 《Journal of clinical anesthesia》1996,8(8):662-665
We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone. 相似文献
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The retina of the goldfish grows by a balloon-like expansion and by the addition of new neurons at the margin. It has been proposed that as a consequence of this expansion the dendritic arbors of ganglion cells in central retina grow in a uniform manner without the addition of new branches. In the present study, we have examined this proposal by comparing the geometries of individual dendritic arbors of large-field ganglion cells from the retinas of small/young and large/old fish. These comparisons were based on measurements of several parameters of dendritic morphology, including number of segments and branches, branch angles, changes in diameter at branch points, and proximal versus distal distribution of arbor length. In addition, we used passive, steady-state cable modeling as an independent method of estimating the functional architectures of small and large dendritic arbors. Our morphometric data indicate that, though they are very different in absolute size, dendritic arbors of small and large ganglion cells have remarkably similar architectures. Analysis with steady-state cable equations indicates that the arbors from small and large cells have equivalent electrotonic lengths and show comparable propagation of synaptic currents. These data are consistent with the hypothesis that dendritic arbors of small and large ganglion cells are scaled versions of one another. We conclude that the growth of these cells during the expansion of the retina is the result of the addition of dendritic mass to an arbor whose basic geometry remains unchanged. 相似文献
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E L Bloomfield 《Military medicine》1992,157(2):59-61
Postoperative nausea and vomiting have been associated with the use of intravenous narcotics, and nitrous oxide may worsen the emetic effects of narcotics. Alfentanil and sufentanil are two synthetic derivatives of fentanyl; alfentanil has a shorter wake-up time than fentanyl, and sufentanil is equivalent to fentanyl. In order to study comparative emetic properties of these two drugs, patients in two different cities were randomly allocated to two different groups and retrospectively compared. Group I received sufentanil N2O/O2 with 0.25% isoflurane. Group II received alfentanil N2O/O2 with 0.25% isoflurane. With group I, the overall incidence of nausea was 31% and of vomiting was 6.2%. For group II, the overall rate for nausea was 38.2% and 8.8% for vomiting. Statistically, there was no significant difference in nausea or vomiting between groups. 相似文献
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SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献
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