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排序方式: 共有475条查询结果,搜索用时 31 毫秒
71.
BACKGROUND: Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition of NEP does not consistently lower blood pressure, even though it increases natriuretic peptide concentrations and causes natriuresis and diuresis. We therefore investigated the direct effects of local inhibition of NEP on forearm resistance vessel tone. METHODS AND RESULTS: Four separate studies were performed, each with 90-minute drug infusions. In the first study, 10 healthy subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/-2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%, P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/-1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30 nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/-2%, P=0.0001). CONCLUSIONS: Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension. The lack of effect of ACE inhibition on the vasoconstriction produced by thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by endothelin-1 and not angiotensin II. These findings may help to explain the failure of systemic NEP inhibition to lower blood pressure. 相似文献
72.
Weiming?Cao Ronald?D.?Haynes Manfred?R.?TrummerEmail author 《Journal of scientific computing》2005,24(3):343-371
We propose an efficient preconditioning technique for the numerical solution of first-order partial differential equations
(PDEs). This study has been motivated by the computation of an invariant torus of a system of ordinary differential equations.
We find the torus by discretizing a nonlinear first-order PDE with a full two-dimensional Fourier spectral method and by applying
Newton’s method. This leads to large nonsymmetric linear algebraic systems. The sparsity pattern of these systems makes the
use of direct solvers prohibitively expensive. Commonly used iterative methods, e.g., GMRes, BiCGStab and CGNR (Conjugate
Gradient applied to the normal equations), are quite slow to converge. Our preconditioner is derived from the solution of
a PDE with constant coefficients; it has a fast implementation based on the Fast Fourier Transform (FFT). It effectively increases
the clustering of the spectrum, and speeds up convergence significantly. We demonstrate the performance of the preconditioner
in a number of linear PDEs and the nonlinear PDE arising from the Van der Pol oscillator 相似文献
73.
Ramaswamy Y Haynes DR Berger G Gildenhaar R Lucas H Holding C Zreiqat H 《Journal of materials science. Materials in medicine》2005,16(12):1199-1205
Biomaterials used in bone regeneration are designed to be gradually resorbed by the osteoclast and replaced by new bone formed
through osteoblastic activity. The aim of the present study is to analyze the role of osteoclasts in the resorption process.
The attachment of human osteoclasts and the appearance of their resorption lacunae, when cultured on either the resorbable
crystalline, calcium orthophosphate materials or on the long-term stable bioceramic material was investigated. The resorbable
materials contain Ca10[K,Na](PO4)7 (AW-Si) and Ca2KNa(PO4)2 (GB14, GB9 & D9/25) as their main crystal phases, however they differ in their total solubility. These differences result
from small variations in the composition. The long-term stable material consist of about 30% fluorapatite beside calcium zirconium
phosphate (Ca5(PO4)3F + CaZr4(PO4)6) and shows a very small solubility. AW-Si has an alkali containing crystalline phase, Ca10[K,Na](PO4). While GB14, GB9 and D9/25 contain the crystalline phase Ca2KNa(PO4)2 with small additions of crystalline and amorphous diphosphates and/or magnesium potassium phosphate (GB14). D9/25 and AW-Si
is less soluble compared to GB14, and GB9 among the resorbable materials. Resorbable and long-term stable materials vary in
their chemical compositions, solubility, and surface morphology. Osteoclasts modified the surface in their attempts to resorb
the materials irrespective of the differences in their physical and chemical properties. The depth and morphology of the resorption
imprints were different depending on the type of material. These changes in the surface structure created by osteoclasts are
likely to affect the way osteoblasts interact with the materials and how bone is subsequently formed. 相似文献
74.
Structural basis of biological nitrogen fixation 总被引:2,自引:0,他引:2
Rees DC Akif Tezcan F Haynes CA Walton MY Andrade S Einsle O Howard JB 《Philosophical transactions. Series A, Mathematical, physical, and engineering sciences》2005,363(1829):971-84; discussion 1035-40
Biological nitrogen fixation is mediated by the nitrogenase enzyme system that catalyses the ATP dependent reduction of atmospheric dinitrogen to ammonia. Nitrogenase consists of two component metalloproteins, the MoFe-protein with the FeMo-cofactor that provides the active site for substrate reduction, and the Fe-protein that couples ATP hydrolysis to electron transfer. An overview of the nitrogenase system is presented that emphasizes the structural organization of the proteins and associated metalloclusters that have the remarkable ability to catalyse nitrogen fixation under ambient conditions. Although the mechanism of ammonia formation by nitrogenase remains enigmatic, mechanistic inferences motivated by recent developments in the areas of nitrogenase biochemistry, spectroscopy, model chemistry and computational studies are discussed within this structural framework. 相似文献
75.
Haynes RK Chan HW Ho WY Ko CK Gerena L Kyle DE Peters W Robinson BL 《Chembiochem : a European journal of chemical biology》2005,6(4):659-667
An economical phase-transfer method is used to prepare 10-arylaminoartemisinins from DHA and arylamines, and artemether, arteether, and artelinate from the corresponding alcohols. In vivo sc screens against Plasmodium berghei and P. yoelii in mice reveal that the p-fluorophenylamino derivative 5 g is some 13 and 70 times, respectively, more active than artesunate; this reflects the very high sc activity of 10-alkylaminoartemisinins. However, through the po route, the compounds are less active than the alkylaminoartemisinins, but still approximately equipotent with artesunate. 相似文献
76.
Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) actions of difenoxin and loperamide are mediated by enteric neurones. An iso-osmotic perfusion solution was circulated around the lumen of the jejunum of anaesthetised rats. Vasoactive intestinal peptide was infused intra-arterially to induce net fluid secretion which was inhibited by difenoxin (ED50, 0.23 mg/kg) and loperamide (ED50, 0.5 mg/kg). However, neither were able to restore the fluid transport rate to the control level of absorption. The antisecretory effects of difenoxin (0.77 mg/kg) and loperamide (0.6 mg/kg) were blocked by the opiate receptor antagonist naloxone (2 mg/kg). Their effects were also abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; with desmethylimipramine given beforehand to protect noradrenergic nerves and enhance 5-HT depletion). The effect of difenoxin was blocked with methiothepin (1 mg/kg) and methysergide (30 micrograms/kg) but not ketanserin (30 micrograms/kg), ritanserin (30 mg/kg), ondansetron (10 micrograms/kg) or ICS 205-930 (3 mg/kg). None of the above 5-HT receptor antagonists modified the antisecretory effect of loperamide. The antisecretory effect of difenoxin but not loperamide was prevented by phentolamine (2 mg/kg) and by pretreatment with 6-hydroxy-dopamine (150 mg/kg total). It is concluded that both difenoxin and loperamide inhibit net fluid secretion by indirect mechanisms. It is proposed that the initial action is on enteric mu-opiate receptors and that this results in the release of 5-HT. In the case of difenoxin, the 5-HT may act on 5-HT1-like receptors to release noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
77.
Fabio Lorenzini Eoghain OHara Shimeng Qian Fabio Marchetti James M. Birbeck Anthony Haynes Alexander J. Blake Graham C. Saunders Andrew C. Marr 《Inorganic chemistry communications》2009,12(10):1071-1073
Rh2(cod)2(μ2-dppm)(μ2-Cl)]BF4 (1) rearranges under carbon monoxide to give [Rh3(μ2-dppm)2(μ2-CO)3(K1-CO)3]BF4 (2). Complex 2 has been structurally characterized by single crystal X-ray crystallography. The hydroformylation activities of 1 and 2 were compared for substrates styrene and 1-hexene and the activity of 2 found to be unexpectedly high. 相似文献
78.
79.
A differential capacitance sensor has been used in the servosystem of a magnetic suspension densimeter to detect the position of a magnetic buoy. This type of sensor has not previously been used in this application. Its design, performance, and advantages are described. 相似文献
80.
Claas Willem Visser Dahlia N. Amato Jochen Mueller Jennifer A. Lewis 《Advanced materials (Deerfield Beach, Fla.)》2019,31(46)
Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high‐throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell–gas core droplets produced using a core–shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low‐viscosity monomer that is rapidly polymerized during the printing process. The transition between open‐ and closed‐cell foams is independently controlled by the gas used, while the foam can be tailored on‐the‐fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out‐of‐plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced. 相似文献