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991.
Hexose-6-phosphate dehydrogenase (H6PD) activity in washed hepatic microsomes from male ICR mice, when assayed with NADP+ and deoxyglucose-6-phosphate, was partially latent. Brief sonication or detergents activated H6PD causing an approximately 4- and 8.5-fold increase in NADPH generation respectively. The sonicated microsomes exhibited H6PD-linked N-demethylase activity toward aminopyrine. This activity was best sustained in the presence of deoxyglucose-6-phosphate, while galactose-6-phosphate, glucose-6-phosphate, and glucose were less effective. Reaction media containing sonicated microsomes, NADP+ and deoxyglucose-6-phosphate also catalyzed N-demethylation of p-chloro-N-methylaniline, N, N-dimethylaniline and nicotine, O-demethylation of p-nitroanisole, p-hydroxylation of aniline, ring hydroxylation of biphenyl at the 2- and 4-positions, dearylation of parathion, and the N-oxidation of N,N-dimethylaniline. In general, the hexose-6-phosphate dehydrogenase-linked monooxygenation rates were 60% or more of those observed in the presence of exogenous NADPH. 相似文献
992.
Stephen H. Rolbin A. F. D. Cole Ernest M. Hew Susan Virgint 《Journal canadien d'anesthésie》1981,28(5):431-435
The effect of lateral positioning and the volume of drug injected on the spread of epidural anaesthesia was assessed in 131 healthy parturients. Epidural injection for anaesthesia was done at the L3-4 interspace and a catheter was inserted into the epidural space after injection of the drug. The patients were randomly assigned to four groups. The doses used were 12 ml of bupivacaine 0.25 per cent and 6 ml of bupivacaine 0.5 percent. Patients were kept in the lateral position in which the block was done (Groups I and III) or turned to the opposite side after completion of the epidural injection (Groups II and IV). Sensory levels and maternal assessment of pain relief were determined fifteen to twenty minutes after injection. All assessments were done by a trained observer who did not know to what group the patient had been allocated. Maintenance of the lateral position after induction of epidural anaesthesia is compatible with satisfactory analgesia for labour. Twelve ml bupivacaine 0.25 per cent provides better analgesia than 6 ml bupivacaine 0.5 per cent although the same mass is injected. The quality of analgesia is improved by turning the patients to the contralateral side after injection of 12 ml bupivacaine 0.25 per cent. 相似文献
993.
These six papers present the effects on human sleep of long-term administration of reserpine (0.50 mg/day), amitriptyline (50 mg/day), chlorpromazine (50 mg/day), chloral hydrate (500 mg/day), and chlordiazepoxide (50 mg/day).This initial paper describes in detail the methodology of the entire study which involves six 60-day drug periods for each subject completing the protocol-one period on each of the five drugs and one period on placebo, in a balanced design. Measures of laboratory sleep, home sleep, and mood were obtained throughout the study.Comparisons between the long placebo-only period of this study and the more usual baseline period-laboratory nights 4-6-revealed a significantly higher total desynchronized sleep time (D-time) and D-time per cent in the placebo period. Other variables were not significantly different. Some clear changes over time within the long placebo period are also described.This work was supported in part by National Institute of Mental Health Grant # MH 14520. 相似文献
994.
995.
De Martino G Edler MC La Regina G Coluccia A Barbera MC Barrow D Nicholson RI Chiosis G Brancale A Hamel E Artico M Silvestri R 《Journal of medicinal chemistry》2006,49(3):947-954
Arylthioindoles (ATIs) that possess a 3-methoxyphenylthio or a 3,5-dimethoxyphenylthio moiety at position 2 of the indole ring were effective tubulin assembly inhibitors, but weak inhibitors of MCF-7 cell growth. ATIs bearing a 3-(3,4,5-trimethoxyphenyl)thio moiety were potent tubulin polymerization inhibitors, with IC(50)s in the 2.0 (35) to 4.5 (37) microM range. They also inhibited MCF-7 cell growth at nanomolar concentrations. The 3,4,5-trimethoxy substituted ATIs showed potencies comparable to those of the reference compounds colchicine and combretastatin A-4 in both tubulin assembly and cell growth inhibition assays. Dynamics simulation studies correlate well with the observed experimental data. Furthermore, from careful analysis of the biological and in silico data, we can now hypothesize a basic pharmacophore for this class of compounds. 相似文献
996.
Hamel E Day BW Miller JH Jung MK Northcote PT Ghosh AK Curran DP Cushman M Nicolaou KC Paterson I Sorensen EJ 《Molecular pharmacology》2006,70(5):1555-1564
Previous studies on the drug content of pelleted tubulin polymers suggest that peloruside A binds in the laulimalide site, which is distinct from the taxoid site. In a tubulin assembly system containing microtubule-associated proteins and GTP, however, peloruside A was significantly less active than laulimalide, inducing assembly in a manner that was most similar to sarcodictyins A and B. Because peloruside A thus far seems to be the only compound that mimics the action of laulimalide, we examined combinations of microtubule-stabilizing agents for synergistic effects on tubulin assembly. We found that peloruside A and laulimalide showed no synergism but that both compounds could act synergistically with a number of taxoid site agents [paclitaxel, epothilones A/B, discodermolide, dictyostatin, eleutherobin, the steroid derivative 17beta-acetoxy-2-ethoxy-6-oxo-B-homo-estra-1,3,5(10)-trien-3-ol, and cyclostreptin]. None of the taxoid site compounds showed any synergism with each other. From an initial study with peloruside A and cyclostreptin, we conclude that the synergism phenomenon derives, at least in part, from an apparent lowering of the tubulin critical concentration with drug combinations compared with single drugs. The apparent binding of peloruside A in the laulimalide site led us to attempt construction of a pharmacophore model based on superposition of an energy-minimized structure of peloruside A on the crystal structure of laulimalide. Although the different sizes of the macrocycles limited our ability to superimpose the two molecules, atom correspondences that were observed were consistent with the difficulty so far experienced in creation of fully active analogs of laulimalide. 相似文献
997.
Sun A Prussia A Zhan W Murray EE Doyle J Cheng LT Yoon JJ Radchenko EV Palyulin VA Compans RW Liotta DC Plemper RK Snyder JP 《Journal of medicinal chemistry》2006,49(17):5080-5092
Measles virus (MV) is one of the most infectious pathogens known. Despite the existence of a vaccine, over 500,000 deaths/year result from MV or associated complications. Anti-measles compounds could conceivably reverse these statistics. Previously, we described a homology model of the MV fusion protein trimer and a putative binding site near the head-neck region. The resulting model permitted the identification of two nonpeptidic entry inhibitors. Here, we present the design, synthesis, and bioevaluation of several series of fusion inhibitors and describe their structure-activity relationships (SAR). Five simply substituted anilides show low-microM blockade of the MV, one of which (AS-48) exhibits IC50 = 0.6-3.0 microM across a panel of wild-type MV strains found in the field. Molecular field topology analysis (MFTA), a 2D QSAR approach based on local molecular properties (atomic charges, hydrogen-bonding capacity and local lipophilicity), applied to the anilide series suggests structural modifications to improve potency. 相似文献
998.
Sturm JM Levine MR Singh A Lash RH 《Ophthalmic plastic and reconstructive surgery》2006,22(2):147-148
This photo-essay illustrates a case of a rapidly enlarging and ulcerated lower eyelid lesion in an HIV-positive man that was thought to be a malignant lesion. The biopsy revealed inclusions consistent with herpesvirus. This clinical entity should be considered in the clinician's differential diagnosis of eyelid lesions. 相似文献
999.
Ernest PH 《Journal of cataract and refractive surgery》2006,32(4):685-686
A 69-year-old man who had uneventful bilateral cataract surgery with visual acuity of 20/15 without correction presented with severe dysphotopsia. Treatment with brimonidine (Alphagan) or pilocarpine did not resolve the symptoms. A multipiece silicone intraocular lens was piggybacked into the sulcus, and the patient no longer reported dysphotopsia. 相似文献
1000.
Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the chemical warfare agent sulfur mustard, has been implicated in the toxicity of sulfur mustard through the inhibition of protein phosphatases in mouse liver cytosol. The absence of any inhibitory activity when TDG was present in assays of pure enzymes, however, led us to investigate the possibility for metabolic activation of TDG to inhibitory compound(s) by cytosolic enzymes. We have successfully shown that mammalian alcohol dehydrogenases (ADH) rapidly oxidize TDG in vitro, but the classic spectrophotometric techniques for following this reaction provided no information on the identity of TDG intermediates and products. The use of proton NMR to monitor the oxidative reaction with structural confirmation by independent synthesis allowed us to establish the ultimate product, 2-hydroxyethylthioacetic acid, and to identify an intermediate equilibrium mixture consisting of 2-hydroxyethylthioacetaldehyde, 2-hydroxyethylthioacetaldehyde hydrate and the cyclic 1,4-oxathian-2-ol. The intermediate nature of this mixture was determined spectrophotometrically when it was shown to drive the production of NADH when added to ADH and NAD. 相似文献