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221.
根据桂枝汤的效应消除半衰期和表观消除半衰期制订给药方案的探讨 总被引:3,自引:0,他引:3
为探讨药效法估测的效应消除半衰期和效量法估测的表观半衰期对合理制订给药方案的意义和作用,以桂枝汤解热和抗炎的药物动力学实验中所得的相应参数值设计了给药方案,观察了它们在提高药效上的作用。结果表明在给药总剂量相等、首次给药同时开始的情况下,以半衰期设计的给药方案组的药效均明显高于习惯的一次给药组;而以效应消除半衰期设计给药方案组药效增强率又高于以表观半衰期设计的方案组。提示效应消除半衰期比表观半衰期似更有实践意义。 相似文献
222.
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol) 总被引:1,自引:0,他引:1
Ikuo Saiki Junya Yoneda Yu Igarashi Miho Aoki Naoto Kusunose Kei-ichi Ono Ichiro Azuma 《Cancer science》1993,84(5):558-565
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”). 相似文献
223.
J. Angerer G. Lehnert 《International archives of occupational and environmental health》1990,61(8):7-10
Summary Stainless steel welders (n = 103) were examined. To estimate external exposure, personal air sampling was used. Internal exposure was quantified by
the determination of nickel levels in erythrocytes, plasma and urine. Men and women (n = 123) were examined for control purposes. In the plasma and erythrocytes of the controls the nickel concentration was below
the level of detection (< 1.81 μg/l). The element concentrations in urine were between < 0.1 and 13.3 μg/l. Of the controls
95% showed nickel levels in urine below 2.2 μg/l (reference value). The average concentration of nickel in the air was 93
± 81 μg/m3. The average concentration of nickel in the plasma samples was 4.9 ± 4.0 μg/l (95th percentile 12.8 μg/L). In erythrocytes
nickel could not be detected. The nickel concentrations in the urine of the welders were 18.5 ± 28.5 μg/l on average (95th
percentile 52.5 μg/l). Only a weak correlation between the nickel levels of plasma and urine could be detected (Curine = 2.07 + 8.45 Cplasma; r = 0.294; p < 0.01). Based on our results and on the reported literature a future limit value for the nickel concentration in urine should
lay between 30 and 50 μg/l. This value corresponds to an external exposure of 500 μg nickel per cubic metre. 相似文献
224.
对全国部分城乡家鼠鼠情监测三年结果的分析表明:城乡家鼠组成均以三大家鼠(褐家鼠、小家鼠、黄胸鼠)为主,其次为食虫目臭鼩鼱~#和黑线姬鼠。五种主要鼠种在家鼠组成中的数量比基本稳定,但三年中城乡少数鼠种间的顺位有所变化。监测结果亦表明,五种主要鼠种的地区分布是:褐家鼠、小家鼠遍布所有监测的省、市、区,同以往文献中遍布全国的说法一致;黄胸鼠分布于黄河以南;食虫目中的臭鼩鼱分布于华中区以南的广大地区。这在以往文献中均已有记载,但以往文献有关黄胸鼠和臭鼩鼱分布的其他说法,则被证实为不确切的。黑线姬鼠的分布范围已超过以往文献中关于分布于东北、华北及长江流域的说法,但以往文献中关于该鼠种遍及全国的说法是否正确,则有待进一步证实。 相似文献
225.
226.
Ross D. King Jonathan D. Hirst Michael J. E. Sternberg 《Perspectives in Drug Discovery and Design》1993,1(2):279-290
Summary Neural networks and machine learning are two methods that are increasingly being used to model QSARs. They make few statistical assumptions and are nonlinear and nonparametric. We describe back-propagation from the field of neural networks, and GOLEM from machine learning, and illustrate their learning mechanisms using a simple expository problem. Back-propagation and GOLEM are then compared with multiple linear regression (using the parameters and their squares) on two real drug design problems: the inhibition ofEscherichia coli dihydrofolate reductase (DHFR) by pyrimidines and the inhibition of rat/mouse tumour DHFR by triazines. 相似文献
227.
K. L. Preston K. L. Preston E. C. Strain G. E. Bigelow J. T. Sullivan K. L. Preston 《Psychopharmacology》1996,123(1):15-25
The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit. Eleven were maintained on methadone 50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who were not physically dependent on opioids and who provided opioid-free urines throughout the study. Each subject received acute cocaine challenge doses of 0, 12.5, 25, and 50 mg intravenously in random order under double-blind conditions in separate test sessions. Physiologic and subject-rated responses were measured before injection and for 2 h after. In the methadone maintenance group, cocaine challenge sessions occurred 15.5 h after the daily methadone dose. There were significant differences between the methadone-dependent and nondependent groups: 1) baseline differences related to chronic methadone administration and not associated with cocaine administration (lower respiration rates and pupil diameter; higher skin temperature) and 2) differences in response to cocaine administration; cocaine-induced increases in subject ratings of Drug Effect, Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater in the methadone maintenance patients compared to the non-dependent group. These results indicate that the positive subjective effects and some physiological effects of cocaine are enhanced in methadone-maintained individuals, suggesting a pharmacological basis for the high rates of cocaine abuse among methadone maintenance patients.Some of these data were presented at the annual meeting of the Committee on Problems of drug Dependence, Keystone, Colorado, June 1992 相似文献
228.
Trenkwalder P, Plaschke M, Aulehner R, Lydtin H. Felodipine or Hydrochlorothiazide/Triamterene for Treatment of' Hypertension in the Elderly: Effects on Blood Pressure, Hypertensive Heart Disease, Metabolic and Hormonal Parameters.
The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (≥70 years) hypertensives (office blood pressure ≥ 60/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months, 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart diesease and showed a neutral metabolic and hormonal profile. 相似文献
The aim of the study was to compare the antihypertensive efficacy of either felodipine or the diuretic combination hydrochlorothiazide/triamterene in a group (n = 65) of elderly (≥70 years) hypertensives (office blood pressure ≥ 60/95 mmHg) with special regard to ambulatory blood pressure monitoring, hypertensive heart disease and metabolic parameters. This was a randomized, double-blind study with a treatment period of 6 months. Reduction of office and 24-hr ambulatory blood pressure was comparable with both treatment regimens; after 6 months, 18 of 29 patients in the felodipine group (62%) and 20 of 27 patients in the diuretic group (74%; p = 0.4) were controlled. While episodes of ischemic type ST-segment depression were significantly reduced in the felodipine group (from 49 to 9 episodes), there was no significant change in the diuretic group (from 24 to 21 episodes). Both regimens decreased left ventricular wall thickness, but the decline in left ventricular muscle mass index was significant only for felodipine. Felodipine did not induce any change in metabolic or hormonal parameters; the diuretic combination significantly increased serum creatinine, uric acid, plasma renin activity, and plasma prorenin. Thus, the antihypertensive efficacy of felodipine and the diuretic combination was comparable in elderly hypertensives; only felodipine, however, improved parameters of hypertensive heart diesease and showed a neutral metabolic and hormonal profile. 相似文献
229.
The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms. 相似文献
230.
Buprenorphine, a partial mu-opioid receptor agonist, has been proposed as a treatment for cocaine abuse. However, studies
in animals have produced conflicting results on the nature of the interaction between buprenorphine and cocaine. In some studies,
buprenorphine attenuated the effects of cocaine and in others it enhanced them. The purpose of the present study was to evaluate
the interaction of buprenorphine and cocaine on the rotational behavior of the nigrally-lesioned rat. Both buprenorphine (0.003–0.1
mg/kg) and cocaine (1.0– 30 mg/kg) alone produced dose-dependent increases in rotational behavior. Buprenorphine produced
long-lasting turning with a peak at 60 min after administration, while cocaine produced turning that peaked immediately after
administration and lasted for about 2 h. To distinguish simple additivity from other possible outcomes, we determined the
relative potency of each drug alone, using a defined level of effect: 150 turns above the saline control in 4 h. This effect
was produced by 10.0 mg/kg cocaine alone and by 0.0175 mg/kg buprenorphine alone. Based on these results, fixed ratio combinations
were tested and the experimentally derived effects were compared to the theoretically additive values, using an isobolographic
analysis. The fixed ratio combinations of the two drugs tested produced turning greater than predicted from simple additivity.
This finding provides statistically-supported evidence for synergism between the actions of buprenorphine and cocaine.
Received: 28 January 1997 / Final version: 7 June 1997 相似文献