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21.
Jack C. Kim 《Archives of pharmacal research》1994,17(3):204-206
A regioselective preparation of 10-methoxy-11-hydroxyaporphine (“Apocodeine,1b”) from (R,S)-10, 11-dihydroxyaporphine(apomorphine,1a) is described. The isopropylidene ketal ring of 10,11-(isopropylidenyldioxy) aporphine (2) obtained by the isopropylidenation of apomorphine, was regioselectively opened by the ten equivalent of trimethylaluminum
to give 10-hydroxy-11-t-butyloxyaporphine (3). The free 10-hydroxyl position of 3 was methylated with methyl p-toluenesulfonate/NaH, and afforded 10-methoxy-11-t-butyloxyaporphine
(4) in high yield. Selective debutylation gave the desired 10-methoxy-11-hydroxyaporphine (“apocodeine”,1b) in good yield. 相似文献
22.
Choc Miles G. Hsuan Francis Honigfeld Gilbert Robinson William T. Ereshefsky Larry Crismon Miles L. Saklad Stephen R. Hirschowitz Jack Wagner Richard 《Pharmaceutical research》1990,7(4):347-351
Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics. 相似文献
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Nathan J Koewler Katie T Freeman Ryan J Buus Monica B Herrera Juan M Jimenez-Andrade Joseph R Ghilardi Christopher M Peters Lucy J Sullivan Michael A Kuskowski Jack L Lewis Patrick W Mantyh 《Journal of bone and mineral research》2007,22(11):1732-1742
A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing. 相似文献
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Five strains of infectious bronchitis virus isolated from commercial chickens from the state of Pennsylvania, USA during the years 1998 and 1999 were studied. The strains were selected for cross-challenge in specific pathogen free chickens and virus neutralization in chick embryos on the basis of partial S1 sequence amino acid identity values. The partial sequences analysed spanned the hypervariable amino terminus region of S1 from amino acid residues 48 to 219, based on the Beaudette strain. Using their S1 identity values, the strains represented a continuum of genetic, and thus antigenic, relationships. When compared with strain PA/5083/99, strain PA/Wolgemuth/98 had high sequence identity (96%) followed by PA/171/99 (85%), PA/5344/98 (70%) and PA/1220/98 (34%). The method of Archetti and Horsfall was used for calculating antigenic relatedness values of virus neutralization tests. The same formula was also applied to the percentage protection values of cross-challenge tests to derive protective relatedness values among the strains. The antigenic relatedness values, protective relatedness values, and the partial S1 sequence identity values were then analysed. The findings indicated partial S1 sequence identity values were more strongly correlated with protective relatedness values and than antigenic relatedness values. 相似文献
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29.
This article focuses on possible psychopharmacological interventions in the immediate post disaster setting. As there is little evidence for the efficacy or effectiveness of such interventions-given the difficulty in performing randomized, double-blind, placebo controlled studies with these populations-the article will delineate the neurobiological basis for pathological sequelae and theoretical drug interventions targeting putative disease mechanisms. 相似文献
30.
RASER: a new ultrafast magnetic resonance imaging method. 总被引:1,自引:0,他引:1
Ryan Chamberlain Jang-Yeon Park Curt Corum Essa Yacoub Kamil Ugurbil Clifford R Jack Michael Garwood 《Magnetic resonance in medicine》2007,58(4):794-799
A new MRI method is described to acquire a T(2)-weighted image from a single slice in a single shot. The technique is based on rapid acquisition by sequential excitation and refocusing (RASER). RASER avoids relaxation-related blurring because the magnetization is sequentially refocused in a manner that effectively creates a series of spin echoes with a constant echo time. RASER uses the quadratic phase produced by a frequency-swept chirp pulse to time-encode one dimension of the image. In another implementation the pulse can be used to excite multiple slices with phase-encoding and frequency-encoding in the other two dimensions. The RASER imaging sequence is presented along with single-shot and multislice images, and is compared to conventional spin-echo and echo-planar imaging sequences. A theoretical and empirical analysis of the spatial resolution is presented, and factors in choosing the spatial resolution for different applications are discussed. RASER produces high-quality single-shot images that are expected to be advantageous for a wide range of applications. 相似文献