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11.
Jürgen Schüttler Donald R. Stanski Paul F. White Anthony J. Trevor Yukio Horai Davide Verotta Lewis B. Sheiner 《Journal of pharmacokinetics and pharmacodynamics》1987,15(3):241-253
The pharmacodynamics of a racemic mixture of ketamine R,S (±)-ketamine and of each enantiomer, S(+)-ketamine and R(–)-ketamine, were studied in five volunteers. The median frequency of the electroencephalogram (EEG) power spectrum, a continuous noninvasive measure of the degree of central nervous system (CNS) depression (pharmacodynamics), was related to measured serum concentrations of drug (pharmacokinetics). The concentration-effect relationship was described by an inhibitory sigmoid Emax pharmacodynamic model, yielding estimates of both maximal effect (Emax) and sensitivity (IC50) to the racemic and enantiomeric forms of ketamine. R(–)-ketamine was not as effective as R,S(±)-ketamine or S(+)-ketamine in causing EEG slowing. The maximal decrease (mean±SD) of the median frequency (Emax)for R(–)-ketamine was 4.4±0.5 Hz and was significantly different fromR,S (±)-ketamine (7.6 ±1.7 Hz) and S(+)-ketamine (8.3±1.9Hz). The ketamine serum concentration that caused one-half of the maximal median frequency decrease (IC50) was 1.8±0.5g/mL for R(–)-ketamine; 2.0±0.5 g/mL for R,S(±)-ketamine; and 0.8±0.4 g/mL for S(+)-ketamine. Because the maximal effect (Emax) of the R(–)-ketamine was different from that of S(+)-ketamine and R,S(±)-ketamine, it was not possible to directly compare the potency (i.e., IC50) of these compounds. Accordingly, a classical agonist/partial-agonist interaction model was examined, using the separate enantiomer results to predict racemate results. Although the model did not predict racemate results well, its failure was not so great as to provide clear evidence of synergism (or excess antagonism) of the enantiomers.This work was supported in part by a Starter Grant from the American Society of Anesthesiologists, the Biomedical Research Support Grant NIH 2S07RR5353-20, 1981, (P.F.W.); and NIH and NIA Research Grants NS-17956 and AG03104 (D.R.S., A.J.T., L.B.S). The research fellowship of Dr. Schüttler was made possible by a NATO Foundation Grant (300-402-511-3), awarded by the German Academic Exchange Service. This study is part of Dr. Schüttler's Habilitation Thesis for the Faculty of Medicine at the University of Bonn, West Germany. Dr. Verotta is a fellow of the program of advanced training established by EEC and Regione Lombardia on leave of absence from Mario Negri Institute of Pharmacological Research, Milan, Italy. 相似文献
12.
目的:探讨黄芪-当归药对(3∶1)对气虚血瘀模型大鼠的益气活血作用,从特征图谱、药效物质辨识、入血成分对比三方面入手,为临床合理用药及复方药效物质辨识与质量控制提供理论依据。方法:使用高效液相色谱法(HPLC)建立黄芪-当归(3∶1)指纹图谱,采用超高效液相色谱-四级杆-静电场轨道阱联用技术(UPLC-Q-Exactive Orbitrap-MS)分析水煎液成分;选用SPF级成年雄性Wistar大鼠,随机分为空白组、模型组、黄芪-当归3∶1组及黄芪-当归5∶1组,每日通过控制食量及凉水游泳制备气虚血瘀模型,同时各组每天给药(水)1次,给药组剂量10.2 g·kg-1,模型组和空白组给予等量的蒸馏水,连续15 d。观察大鼠一般状况;记录各组大鼠体质量,全血及血浆黏度,胸腺指数和脾脏指数,血清中三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、大鼠血管性血友病因子(vWF)水平及ATP/ADP值;苏木素-伊红(HE)及扫描电镜观察血管内皮形态;UPLC-QExactive Orbitrap-MS分析血清中的原型及代谢成分。结果:建立了黄芪-当归(3∶1)指纹图谱;UPLC-Q-Exactive ... 相似文献
13.
This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments. 相似文献
14.
目的观察京尼平苷预防给药对地鼠胆固醇结石形成的影响.方法用高脂肪高蛋白致石饲料造成地鼠胆固醇结石模型,阳性对照药物熊去氧胆酸80mg/kg和京尼平苷50,100mg/kgig,每天预防给药,给药30d后作胆囊内容物涂片检查观察地鼠的成石率,检测胆汁脂类成分计算胆汁成石指数.结果模型组的成石率为100%,成石指数(LI)大于1;京尼平苷50和100mg/kg组的成石率分别为40%(P<0.05)和25%(P<0.01),LI均小于1,熊去氧胆酸组的成石率与LI与京尼平苷100mg/kg组相近.结论京尼平苷对地鼠胆固醇结石的形成可能具有抑制作用. 相似文献
15.
熟地黄药效物质基础研究进展 总被引:2,自引:1,他引:1
熟地黄为玄参科植物地黄Rehmannia glutinosa新鲜或干燥块根的炮制加工品,具有补血滋阴、益精填髓等功效。熟地黄是中药“滋阴”作用最具代表的药味之一,也被称之为“至阴之药”。熟地黄配伍相关经典方剂被广泛应用于治疗肝肾阴虚导致的各种临床疾病,包括糖尿病相关疾病、神经系统疾病、骨关节炎相关疾病、妇科相关疾病等。基于近年来发表的文献,对熟地黄化学成分、活性成分的药理作用、方剂配伍条件下的药效物质的基础研究进展进行综述,以期为熟地黄的深入研究提供参考。 相似文献
16.
With a view to ultimately identifying factors involved in the development of pancreatic insulin cells, we have cultured dorsal
pancreatic buds from 5-day chick embryos on a basement membrane matrix (Matrigel) in a serum-free medium supplemented with
selected factors. The endodermal components of the buds were freed of almost all the mesenchyme so as to eradicate as much
as possible of this source of some such factors. In 7-day cultures, insulin and glucagon cells were demonstrated immunocytochemically;
numbers of insulin cells were expressed as a percentage of insulin plus glucagon cell counts. Our standard medium contained
insulin. Addition of tri-iodothyronine to this medium did not increase the proportion of insulin cells, but in combination
with raised concentrations of glucose and essential amino acids it improved somewhat the marked increase previously recorded
for these nutrient conditions. Omission of insulin from the standard medium greatly reduced the proportion of these cells;
substitution of insulin by insulin-like growth factor I increased the proportion considerably more than did insulin. To test
for an overall effect of growth factors, explants were cultured in standard medium on Matrigel containing reduced amounts
of growth factors: the proportion of insulin cells proved to be increased over that reached on normal Matrigel. The suspicion
that transforming growth factor β1, a component of Matrigel, might act to reduce the proportion of insulin cells was tested
and found to be correct. It is suggested that the different factors studied here may affect either or both of proliferation
and determination in the differentiation pathway of insulin vis-à-vis glucagon cells.
Accepted: 13 March 1998 相似文献
17.
根据三种估算药动学和药效学结合模型参数的方法编制了软件。参数法包括十个药动学模型和三种药效学模型,可以同时求算药动学和药效学参数;非参数药效模型法不必预先假设药效学模型就可估算出反映药物效应的消除速率常数(K_(eo));非参数药效模型法中,药动学模型也用非参数方法描述,只要输入药动—药效数据就可求出K_(ro)。对6例吸入大麻的健康志愿者的药动—药效数据,用以上方法进行验算,结果表明三种方法各有优点,应比较使用。 相似文献
18.
Pierre Gianello Jonathan Fishbein Tatiana Besse Thierry Gustin Charles Chatzopoulos Jean-Marie Ketelslegers Luc Lambotte Jean-Paul Squifflet 《Transplant international》1994,7(1):11-16
In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n=12) or University of Wisconsin (UW) solution (n=6) for 10 min. Each kidney was then harvested and stored at 4°C in its respective solution. After 24 and 48 h of cold storage, the following vasoactive substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B2) (TxB2), and prostaglandin I2 (PGI2). After 24 h in EC solution, left kidneys uniformly produced significantly higher concentrations of each vasoactive substance than right kidneys: ET 1.64±0.3 pg/ml vs 0.82±0.1 pg/ml (P0.009); A-II 20.8±6.2 pg/ml vs 7.75+2.3 pg/ml (P0.007); TxB2 100.8±17.7 pg/ml vs 40.1±11.7 pg/ml (P0.04); PGI2 638.3±41.1 pg/ml vs 318.3±36.4 pg/ml (P0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to produce TxB2 and prostacyclins during the 24–48 h period. In the UW solution, basal levels of ET and A-II were lower than those in EC solution, but similarly increased after initial ischemia. At 24 h, the concentrations produced by the left and right kidneys were as follows: ET 0.66±0.1 pg/ml vs 0.48±0.1 pg/ml (P0.14); A-II 10.36±3.7 pg/ml vs 2.14±0.7 pg/ml (P0.006); TxB2 178±53 pg/ml vs 52±23.1 pg/ml (P0.001); and PGI2 448.3±49 pg/ml vs 323±44.3 pg/ml (P0.01), respectively. After 48 h, the range of concentrations of each substance was similar to that obtained after 24 h. In further studies, the concentrations of ET and A-II were measured in solution previously used to preserve human kidneys (n=7). The mean concentration of ET and A-II in these samples was 3.82±1.14 pg/ml and 21.3±9.2 pg/ml, respectively, whereas in control media both substances were below the limits of detection. These results demonstrate that vasoconstrictive substances can be measured in the preservation media after a kidney has been stored cold and that higher concentrations are found when the organ has been subjected to prior normothermic ischemia. The measurement of these vasoactive substances before transplantation may reveal that the kidney has been subjected to previous ischemic events. Moreover, these vasoactive substances could be involved in the early recovery of renal function after kidney transplantation. 相似文献
19.
Pigeau R Naitoh P Buguet A McCann C Baranski J Taylor M Thompson M MacK I 《Journal of sleep research》1995,4(4):212-228
SUMMARY Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations. 相似文献
20.
铬结合物在铬中毒性肝损害中的作用 总被引:1,自引:0,他引:1
目的了解各种铬结合物与肝损害的关系。方法在铬中毒性肝损害的大鼠模型中,采用SephadexG50凝胶层析技术,对肝中铬结合物进行分离和测定。结果铬染毒大鼠肝组织中,除可检出高分子铬结合物(HMWCr,相对分子质量(MW)70000~12500)及低分子铬结合物(LMWCr,MW12500~500)外,还发现对照组未检出的小分子铬结合物(MMWCr,MW<500)。随染毒时间延长,肝损害加重,三者肝中分布变化明显:HMWCr由22.2%增至37.0%;MMWCr由2.2%增至5.0%;LMWCr则从75.6%降至58.0%。结论LMWCr可能与铬的解毒有关;MMWCr的出现并增多反映了机体形成LMWCr能力的紧张;MMWCr可能是攻击靶器官的主要活性因素。 相似文献