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61.
Gill S Gill R Lee SS Hesketh JC Fedida D Rezazadeh S Stankovich L Liang D 《Assay and drug development technologies》2003,1(5):709-717
Ion channels have been identified as therapeutic targets in various disorders, such as cardiovascular disease, neurological disease, and cystic fibrosis. Flux assays to detect functional ionic flux through ion channels are becoming increasingly popular as tools for screening compounds. In an optimized flux assay, modulation of ion channel activity may produce readily detectable changes in radiolabeled or nonradiolabeled ionic flux. Technologies based on flux assays are currently available in a fully automated high throughput format for efficient screening. This application offers sensitive, precise, and reproducible measurements giving accurate drug rank orders matching those of patch clamp data. Conveniently, the flux assay is amenable to adaptation for different ion channels, such as potassium, sodium, calcium, and chloride channels, by using suitable tracer ions. The nonradiolabeled rubidium-based flux assay coupled with the ion channel reader (ICR) technology has become very successful in ion channel activity analysis and is emerging as a popular technique in modern drug discovery. 相似文献
62.
The present ethnobotanical field study conducted during summer 2003 in two distinct regions of the Cilento National Park (Mt Vesole and Ascea) documents the local use of 90 different plant species for medicinal, food and domestic purposes. Overall, 59 people native to the area were interviewed, and 883 use-reports have been recorded. The scientific names, local names, plant parts used, preparation and administration processes are given and compared with practices in other Italian regions. In total, 63 species are documented as medicinal, 49 as food, and 22 as craft plants. Over 40% of all species are used in more than one category and over half of the food plants are also used for medicinal purposes. In general the recorded species are well known in the traditional phytotherapy of Campania and Italy. However, some uses are unusual and are discussed in detail. 相似文献
63.
The effects of aging on the secretory function of hypothalamic granules containing luteinizing hormone releasing hormone (LHRH) were examined, using chelated copper as a test substance. Granules prepared from old and young female rats were each incubated with various concentrations of CuATP and the kinetic constants of LHRH release estimated. The LHRH content of the hypothalamus of old female rats (3.4± 0.1 ng; mean±S.E.; n=3 determinations) was lower than that of young female rats (4.7±0.1 ng;n=3). CuATP-stimulated LHRH release (pg/hypothalamus) from granules isolated from old animals was significantly (p<0.001) lower than that from granules isolated from young animals; Vmax being 58.5±1.6 pg (n=36) and 76.7±2.7 pg (n=34) of LHRH released/min, respectively. In contrast, the fractional amount of CuATP-stimulated of LHRH from granules isolated from old and young rats was similar; Vmax being 60±0.5% and 62±1% of granule LHRH released respectively. In addition, the apparent Km for CuATP-stimulated release of LHRH from granules of old and youn rats was also similar, 5.1 and 5.5. μM copper, respectively. These results are suggestive that aging does not alter the responsiveness of LHRH-containing granules to a secretion-stimulus such as copper but it does alter the capacity (amount) of peptide released. 相似文献
64.
Rezazadeh S Claydon TW Fedida D 《The Journal of pharmacology and experimental therapeutics》2006,317(1):292-299
The effect of Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) on voltage-gated ion channels is widely studied through the use of specific CaMK II blockers such as 2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine (KN-93). The present study demonstrates that KN-93 is a direct extracellular blocker of a wide range of cloned Kv channels from a number of different subfamilies. In all channels tested, the effect of 1 microM KN-93 was independent of CaMK II because 1 microM2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, phosphate (KN-92), an inactive analog of KN-93, caused similar inhibition of currents. In addition, dialysis of cells with 10 microM CaMK II inhibitory peptide fragment 281-301 (CIP) had no effect on current kinetics and did not prevent the inhibitory effect of KN-93. The IC(50) for block of the Kv1.5 channel (used as an example to determine the nature of KN-93 block) was 307 +/- 12 nM. KN-93 blocked open channels with little voltage dependence that did not alter the V(1/2) of channel activation. Removal of P/C-type inactivation by mutation of arginine 487 to valine in the outer pore region of Kv1.5 (R487V) greatly reduced KN-93 block, whereas enhancement of inactivation induced by mutation of threonine 462 to cysteine (T462C) increased the potency of KN-93 by 4-fold. This suggested that KN-93 acted through promotion and stabilization of C-type inactivation. Importantly, KN-93 was ineffective as a blocker when applied intracellularly, suggesting that CaMK II-independent effects of KN-93 on Kv channels can be circumvented by intracellular application of KN-93. 相似文献
65.
66.
Daniel Werry Jodene Eldstrom Zhuren Wang David Fedida 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(11):E996
Coassembly of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with potassium voltage-gated channel, Isk-related family, member 1 (KCNE1) the delayed rectifier potassium channel IKs. Its slow activation is critically important for membrane repolarization and for abbreviating the cardiac action potential, especially during sympathetic activation and at high heart rates. Mutations in either gene can cause long QT syndrome, which can lead to fatal arrhythmias. To understand better the elementary behavior of this slowly activating channel complex, we quantitatively analyzed direct measurements of single-channel IKs. Single-channel recordings from transiently transfected mouse ltk− cells confirm a channel that has long latency periods to opening (1.67 ± 0.073 s at +60 mV) but that flickers rapidly between multiple open and closed states in non-deactivating bursts at positive membrane potentials. Channel activity is cyclic with periods of high activity followed by quiescence, leading to an overall open probability of only ∼0.15 after 4 s under our recording conditions. The mean single-channel conductance was determined to be 3.2 pS, but unlike any other known wild-type human potassium channel, long-lived subconductance levels coupled to activation are a key feature of both the activation and deactivation time courses of the conducting channel complex. Up to five conducting levels ranging from 0.13 to 0.66 pA could be identified in single-channel recordings at 60 mV. Fast closings and overt subconductance behavior of the wild-type IKs channel required modification of existing Markov models to include these features of channel behavior. 相似文献
67.
Arwa Battah Hossam Abed Dema Shamoon Theodore DaCosta Iyad Farouji Andre Fedida 《Radiology Case Reports》2022,17(9):3286
Lymphoma in the gastrointestinal tract most commonly occurs in the stomach, small intestine and around the ileocecal region. Usually gastrointestinal lymphoma occurs secondary to widespread nodal disease and is rarely found to be the primary site. Of the different types of lymphoma, diffuse large B-cell non-Hodgkin''s lymphoma makes up the majority of lymphomas in the gastrointestinal tract. Primary colorectal lymphoma is even less common and accounts for 3% of all gastrointestinal lymphomas and to our knowledge, gastrointestinal lymphoma involving 2 different regions in the GI tract has not been discussed in the literature. Herein, we are presenting a rare case of diffuse large B-cell lymphoma presenting as a malignant mass in both the duodenum and ascending colon. 相似文献