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排序方式: 共有378条查询结果,搜索用时 31 毫秒
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Inactivation of platelet-activating factor by a putative acetylhydrolase from the gastrointestinal nematode parasite Nippostrongylus brasiliensis. 下载免费PDF全文
The adult stage of Nippostrongylus brasiliensis, a strongyloid parasite of the gastrointestinal tract of rats, released a product during in vitro culture which functionally inhibited platelet-activating factor (PAF), measured by its ability to mediate platelet aggregation. The extent of inhibition was proportional to the concentration of excretory/secretory (ES) products and the duration of preincubation with PAF prior to the assay of biological activity. The inhibitory activity was heat labile and was specific for PAF, as incubation of ES products with thrombin showed no diminution of platelet aggregation. Experiments using radiolabelled preparations of PAF demonstrated that the acetyl group esterified at the sn-2 position of the glycerol backbone was liberated on incubation with ES products, indicative of an acetylhydrolase activity. This activity was susceptible to inhibition by DFP, partial inhibition by eserine, but was resistant to PMSF and TPCK at concentrations which inhibit serine proteases. 相似文献
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R Dixon AM Hughes K Nairn M Sellers JV Kemp RA Yates 《Cephalalgia : an international journal of headache》1998,18(7):468-475
Zolmitriptan (ZomigTM ) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination. 相似文献
5.
Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10−4 M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle. 相似文献
6.
Needle biopsy of renal allografts: comparison of two techniques 总被引:2,自引:0,他引:2
Bogan ML; Kopecky KK; Kraft JL; Holladay AO; Filo RS; Leapman SB; Thomalla JV 《Radiology》1990,174(1):273-275
Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications. 相似文献
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Covalent binding of isomeric benzo[a]pyrene diol-epoxides to DNA 总被引:1,自引:0,他引:1
We have compared the abilities of two diol-epoxide derivativesof benzo[a]pyrene (B[a]P) to bind covalently to DNA in a simplein vitro system. Purified DNA in aqueous solution was allowedto react with (±)-7, 8ß-dihydroxy-9ß,10ß-oxy-7,8,9,10-tetrahydroB[a]P (BPDE) or with (±)-9,10ß-dihydroxy-7,8-oxy-7,8,9,10-tetrahydroB[a]P (reverseBPDE) to completion. After repurification of the DNA, bindingwas detected by fluorescence spectroscopy or by absorbance spectroscopy.Both BPDE and reverse BPDE but not their hydrolysis productsexhibited binding which increased linearly with increasing diolepoxide concentration. When DNA modified by reverse BPDE wasenzymatically hydrolysed, two major fluorescent deoxyribonucleoside-adductswere detected by reverse phase h.p.l.c. These were separablefrom the major adduct obtained from BPDE-modified DNA and fromthe major products obtained by hydrolysis of reverse BPDE inthe absence of DNA. Absorbance and fluorescence spectroscopyof modified native DNA suggested that the pyrene nucleus ofreverse BPDE but not of BPDE was intercalated in the DNA doublehelix. This suggestion was supported by fluorescence-quenchingstudies. In the presence of increasing DNA concentrations, covalentbinding of both diol epoxides increased towards an apparentmaximum. Double reciprocal analysis of the data indicated amaximum binding level of 5% of the total dose for BPDE and 4%for reverse BPDE. This suggests that for both diol epoxidesthe ratio of the rate constants for covalent binding and forDNA-enhanced hydrolysis are nearly the same. Covalent bindingof reverse BPDE to DNA was effectively blocked by low concentrationsof Mg2+, suggesting that formation of a non-covalent intercalationcomplex may be a prerequisite for covalent reaction. 相似文献
9.
JV Aranda A Varvarigou K Beharry R Bansal C Bardin H Modanlou A Papageorgiou S Chemtob 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(3):289-293
The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t 1/2 beta was 30.5 ± 4.2 h, elimination rate constant (kel ) was 0.032 ± 0.004 h-1 plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy. 相似文献
10.
PT Clayton M Doig S Ghafari C Meaney C Taylor JV Leonard M Morris AW Johnson 《Archives of disease in childhood》1998,79(2):109-115
OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK. 相似文献