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991.
HR Arias 《Canadian Metallurgical Quarterly》1995,12(4):339-347
It was previously demonstrated that high concentrations of cholinergic agonists such as acetylcholine (ACh), carbamylcholine (CCh), suberyldicholine (SubCh) and spin-labelled acetylcholine (SL-ACh) displaced quinacrine from its high-affinity binding site located at the lipid-protein interface of the nicotinic acetylcholine receptor (AChR) (Anas, H. R. and Johnson, D. A. (1995) Biochemistry, 34, 1589-1595). In order to account for the agonist self-inhibitory binding site which overlaps, at least partially, with the quinacrine binding site, we determined the partition coefficient (Kp) of these agonists relative to the local anaesthetic tetracaine in AChR native membranes from Torpedo californica electric organ by examining (1) the ability of tetracaine and SL-ACh to quench membrane-partitioned 1-pyrenedecanoic acid (C10-Py) monomer fluorescence, and (2) the ability of ACh, CCh and SubCh to induce an increase in the excimer/monomer ratio of C10-Py-labelled AChR membrane fluorescence. To further assess the differences in agonist accessibility to the quinacrine binding site, we calculated the agonist concentration in the lipid membrane (CM) at an external agonist concentration high enough to inhibit 50% of quinacrine binding (IC50), which in turn was obtained by agonist back titration of AChR-bound quinacrine. Initial experiments established that high agonist concentrations do not affect either transmembrane proton concentration equilibria (pH) of AChR membrane suspension or AChR-bound quinacrine fluorescence spectra. The agonist membrane partitioning experiments indicated relatively small (< or = 20) Kp values relative to tetracaine. These values follow the order: SL-ACh>SubCh>CCh-ACh. A direct correlation was observed between Kp and the apparent inhibition constant (Ki) for agonists to displace AChR-bound quinacrine. Particularly, agonist with high KpS such as SL-ACh and SubCh showed low Ki values, and this relationship was opposite for CCh and ACh. The calculated CM values indicated significant (between 7 and 54 mM) agonist accessibility to lipid membrane. By themselves, these results support the conjecture that agonist self-inhibition seems to be mediated by the quinacrine binding site via a membrane approach mechanism. The existence of an agonist self-inhibitory binding site, not located in the channel lumen would indicate an allosteric mechanism of ion channel inhibition; however, we can not discard that the process of agonist self-inhibition can also be mediated by a steric blockage of the ion channel. 相似文献
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HR Taylor 《Canadian Metallurgical Quarterly》1976,82(5):733-735
Thirty-two tissue blocks removed during trabeculectomy were examined histologically, 16 by both scanning electron microscopy and light microscopy, and 16 by light microscopy alone. Trabecular meshwork was identified in 27 specimens (84.3%) and Schlemm's canal in 17 (53%), each found with equal frequency by either technique. Ciliary muscle was identified in eight of 32 of specimens (25%) examined by light microscopy, but was present in 12 of 16 specimens (75%) examined by scanning electron microscopy. The identification of these specific anatomical structures did not correlate with the postoperative outcome. These findings support the contention that trabeculectomy is a filtering procedure. 相似文献
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999.
John G. Thompson Ray L. Withers Bruce G. Hyde 《Journal of the American Ceramic Society》1987,70(12):383-C
The results of an investigation of the system Ba2 SiO4 –Ca2 SiO4 by powder X-ray and electron diffraction suggest a greater complexity than supposed hitherto. The previously recognized phases α, α' h α' l , X, T, and the newly reported Y have room-temperature structures that are modulated distortions of hexagonal (or pseudohexagonal) parent structures. Each displays characteristic and distinctive modulations. The phases are more readily distinguished in this way than by their unit-cell dimensions and compositions which, for a given phase, can vary with bulk starting composition and thermal history. 相似文献
1000.
AIM: To review the various pharmacological approaches currently proposed for the treatment of hypertension. RESULTS: With the evolution of pharmacological treatment of hypertension, various classes of agent (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, calcium antagonists and alpha 1-blockers) have become available for the initiation of antihypertensive therapy. As monotherapy, each type of agent will normalize blood pressure in about half of all hypertensive patients. Replacing one drug with another that acts through a different mechanism improves the probability of controlling blood pressure. Another way to increase the number of responders is to increase the dose; however, this often results in more side effects. A preferable way of improving efficacy is to combine low doses of drugs that have different impacts on the cardiovascular system, thus opposing the compensatory responses that tend to limit the blood pressure drop. CONCLUSION: Low-dose drug combinations are generally well tolerated and the treatment of hypertension can be simplified by using fixed-dose combinations. These combinations have the potential to become a valuable alternative in the initiation of antihypertensive therapy. 相似文献