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Clinical pharmacology in Eastern European countries. 东欧国家的临床药理学。
A Simonić, B Vrhovac

The current status of clinical pharmacology (CP) in the countries of the former Eastern block is presented. The difficulties in obtaining an accurate comparative view are pointed out. CP is unevenly developed in Eastern European countries and the number of hours devoted to basic/clinical pharmacology differs considerably 100/nil to 240/50. The same is true for the orientation of clinical pharmacology, where present. It is mainly basic in only a few countries (Rumania, Turkey, some parts of the former Yugoslavia) and mainly clinical in Czecho-Slovakia, Croatia, Hungary, Poland, Greece. The number of CP units and CP specialists varies greatly as well (from none to more than 10 per country). The awareness that CP, in many countries is still young and the branch of (clinical) medicine is of great importance, not only for rational pharmacotherapy but also for other services as well, education and research is growing. In spite of the fact that the present status of CP in Eastern European countries is generally unsatisfactory, there are realistic chances that in the (near?) future, CP will develop to match the activities now present in the more developed countries.

临床药理学(CP)的现状,在国家的前东部块提出。指出了获得准确的比较观点的困难。东欧国家的CP发展不均衡,用于基础/临床药理学的小时数相差很大,从100/ 0到240/50不等。临床药理学的方向也是如此。它仅在少数国家(罗马尼亚、土耳其、前南斯拉夫的一些地区)主要是基本的,在捷克斯洛伐克、克罗地亚、匈牙利、波兰、希腊主要是临床的。CP单位和CP专家的数量也有很大差异(每个国家从没有到超过10个)。人们越来越认识到,临床医学在许多国家还很年轻,不仅对合理的药物治疗,而且对其他服务、教育和研究都非常重要。尽管东欧国家目前的CP状况总体上不令人满意,但在(不久的?)将来,CP将发展到与目前在较发达国家的活动相匹配的现实机会。
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引用次数: 0
Effect of food on pravastatin pharmacokinetics and pharmacodynamics. 食物对普伐他汀药代动力学和药效学的影响。
H Y Pan, A R DeVault, D Brescia, D A Willard, M E McGovern, D B Whigan, E Ivashkiv

The pharmacokinetics and pharmacodynamics of pravastatin 20 mg administered twice daily when taken with or one hour before meals were evaluated in 24 hypercholesterolemic men in an 8-week, open-label, randomized, two-way crossover study. The bioavailability of pravastatin was reduced significantly (p < or = 0.001) when it was taken with meals (AUC dropped 31% and Cmax dropped 49%), and mean Tmax increased 50% (p < or = 0.01). The mean elimination t1/2 was unaffected by taking pravastatin with food. However, reductions in mean total cholesterol and low density lipoprotein cholesterol were identical whether pravastatin was given with or before meals. In both treatment groups, total cholesterol and low-density lipoprotein cholesterol were significantly reduced from baseline (p < 0.001). These results indicate that although the bioavailability of pravastatin is reduced when taken with meals, the lipid-lowering efficacy of pravastatin is not altered. It can be concluded that pravastatin can be ingested without regard to meal time.

在一项为期8周的开放标签、随机、双向交叉研究中,对24名高胆固醇血症男性患者进行了普伐他汀20mg的药代动力学和药效学评估,每日两次,随餐服用或餐前一小时服用。与餐同服普伐他汀显著降低生物利用度(AUC下降31%,Cmax下降49%),平均Tmax增加50% (p <或= 0.01)。平均消除t1/2不受普伐他汀与食物一起服用的影响。然而,无论是餐前还是餐后服用普伐他汀,平均总胆固醇和低密度脂蛋白胆固醇的降低都是相同的。在两个治疗组中,总胆固醇和低密度脂蛋白胆固醇较基线显著降低(p < 0.001)。这些结果表明,虽然普伐他汀的生物利用度在进餐时降低,但普伐他汀的降脂功效并没有改变。由此可见,普伐他汀可以不考虑进餐时间而摄入。
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引用次数: 0
Acute effects of conventional oral dose of disopyramide on left atrial and ventricular functions. 常规口服剂量双丙酰胺对左心房和心室功能的急性影响。
M Arakawa, H Miwa, T Noda, K Kagawa, K Nishigaki, Y Ito, T Kawada, S Hirakawa

Disopyramide, an antiarrhythmic drug, is known to impair cardiac function, but acute cardiac effects of conventional oral dose of disopyramide are not well known. To examine the extent of acute cardiac effects of daily oral dose of disopyramide, we gave 150 mg of disopyramide to thirteen patients with normal or impaired cardiac function, and observed cardiac function on an hourly basis for 3 hours after baseline period. The serum level of disopyramide reached a therapeutic level (2.0-5.0 micrograms/ml) mostly 1 hour after administration. Doppler-echocardiographically determined left ventricular ejection fraction, and the ratio of the peak early filling velocity to the peak atrial filling velocity in left ventricular inflow velocity remained unchanged throughout the experimental period. Other hemodynamic variables, such as blood pressure and heart rate remained unchanged. We conclude that daily oral dose of disopyramide appears to have no significant effects on cardiac function after administration. Disopyramide seems to be safe and may not be necessarily withheld from patients who need it, when hemodynamic variables are to be measured.

已知抗心律失常药物双吡脲会损害心功能,但常规口服双吡脲的急性心脏效应尚不清楚。为了研究每日口服双酰胺对急性心脏的影响程度,我们给13例心功能正常或受损的患者服用150 mg双酰胺,并在基线期后3小时内每小时观察一次心功能。在给药后1小时,患者血清双哌替啶水平基本达到治疗水平(2.0 ~ 5.0微克/ml)。多普勒超声心动图测定左室射血分数,实验期间左室流入流速中早期充血速度峰值与心房充血速度峰值之比保持不变。其他血液动力学变量,如血压和心率保持不变。我们的结论是,每日口服双双酰胺剂量似乎对心功能没有显著影响。当需要测量血流动力学变量时,二丙酰胺似乎是安全的,可能不一定不给需要它的患者使用。
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引用次数: 0
The effects of different doses of sodium bicarbonate on the absorption and activity of non-micronized glibenclamide. 不同剂量碳酸氢钠对非微粉格列苯脲吸收及活性的影响。
K T Kivistö, P Lehto, P J Neuvonen

The effects of different doses of sodium bicarbonate on the absorption and activity of non-micronized glibenclamide were studied in six healthy volunteers, using a randomized crossover design with four phases. The subjects ingested a single dose of non-micronized glibenclamide (2.5 mg) with 150 ml of water or with 150 ml of water containing 0.3, 1.0 or 3.0 g of sodium bicarbonate. Plasma concentrations of glibenclamide, insulin and glucose were measured. Coadministration of 1.0 or 3.0 g of sodium bicarbonate with non-micronized glibenclamide increased the area under the plasma glibenclamide concentration-time curve (AUC) from 0 to 1 h 30-fold (p < 0.05) and 38-fold (p < 0.05), respectively. The 1.0- and 3.0-g doses of sodium bicarbonate also increased the AUC of plasma glibenclamide from 0 to 2 h, about 3-fold (p = 0.05 and 0.07, respectively). The peak plasma concentration, peak time and total extent of absorption of glibenclamide and the insulin and glucose responses were not significantly altered by any of the doses of sodium bicarbonate studied. Concomitant ingestion of 1.0 or 3.0 g of sodium bicarbonate and non-micronized glibenclamide greatly increased the early bioavailability of glibenclamide. However, this interaction did not alter the activity of glibenclamide.

采用四期随机交叉设计,研究了不同剂量碳酸氢钠对非微粉格列本脲吸收和活性的影响。受试者用150ml水或150ml含有0.3、1.0或3.0 g碳酸氢钠的水摄入单剂量非微粉格列本脲(2.5 mg)。测定血浆中格列本脲、胰岛素和葡萄糖的浓度。1.0或3.0 g碳酸氢钠与非微粉格列本脲共给药可使血浆格列本脲浓度-时间曲线下面积(AUC)分别增加30倍(p < 0.05)和38倍(p < 0.05)。1.0和3.0 g剂量的碳酸氢钠也使血浆格列苯脲的AUC从0 ~ 2 h增加了约3倍(p分别= 0.05和0.07)。血浆峰浓度、峰时间和格列苯脲吸收的总程度以及胰岛素和葡萄糖反应均未因任何剂量的碳酸氢钠而显著改变。同时摄入1.0或3.0 g碳酸氢钠和非微粉格列本脲可大大提高格列本脲的早期生物利用度。然而,这种相互作用并没有改变格列本脲的活性。
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引用次数: 0
Selective determination of non-enzymatic glycosylated serum albumin as a medium term index of diabetic control. 选择性测定非酶糖化血清白蛋白作为糖尿病控制的中期指标。
W Wörner, S Pfleiderer, N Rietbrock

Serum proteins are non-enzymatically glycosylated dependent on the concentration of free glucose and measurements of their concentration are used to control diabetic carbohydrate metabolism. Eight patients with insulin-dependent diabetes mellitus (IDDM) and 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) with glycosylated hemoglobin levels of at least 10.5% were studied during a 6-week period of antidiabetic therapy. Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP) were measured weekly using an affinity chromatography procedure. The fructosamine test (FA) and the measurement of mean blood glucose (MBG) were also carried out weekly. Glycosylated hemoglobin and its glucose adduct HbA1c were determined at 14-day intervals (HPLC-method). All measured parameters decreased during the period of the study. The correlation coefficients for the glycosylated proteins versus the MBG determined one week earlier were highest for GSA [IDDM: r(GSA/MBG-1) = 0.726, p < 0.001 for the single values and 0.984, p < 0.001 for the mean values; NIDDM: r (GSA/MBG-1) = 0.636, p < 0.001 for the single values and 0.986, p < 0.001 for the mean values]. The differences between the IDDM and NIDDM group probably occurred because 6 NIDDM patients were taking glibenclamide (7.0-10.5 mg/day) which is known to inhibit the glycosylation reaction of albumin. The fructosamine test is more prone to interferences than the selective determination of GSA. GSA determination therefore, gives precise data in medium term diabetic control.

血清蛋白的非酶性糖基化依赖于游离葡萄糖的浓度,其浓度的测量可用于控制糖尿病的碳水化合物代谢。在为期6周的降糖治疗期间,研究了8例胰岛素依赖型糖尿病(IDDM)和8例糖化血红蛋白水平至少为10.5%的非胰岛素依赖型糖尿病(NIDDM)患者。糖基化血清白蛋白(GSA)和糖基化血清总蛋白(GSP)每周使用亲和色谱法测定。每周进行果糖胺试验(FA)和平均血糖(MBG)测定。每隔14天测定糖化血红蛋白及其葡萄糖加合物HbA1c(高效液相色谱法)。在研究期间,所有测量参数都有所下降。糖基化蛋白与1周前测定的MBG的相关系数在GSA中最高[IDDM: r(GSA/MBG-1) = 0.726,单个值p < 0.001,平均值0.984,p < 0.001];NIDDM: r (GSA/MBG-1) = 0.636,单个值p < 0.001,平均值0.986,p < 0.001。IDDM组和NIDDM组之间的差异可能是因为6例NIDDM患者服用了格列本脲(7.0-10.5 mg/天),已知格列本脲可以抑制白蛋白的糖基化反应。果糖胺试验比选择性测定GSA更容易受到干扰。因此,测定GSA可提供中期糖尿病控制的精确数据。
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引用次数: 0
Iron protein succynilate in the treatment of iron deficiency: potential interaction with H2-receptor antagonists. 琥珀酸铁蛋白治疗缺铁:与h2受体拮抗剂的潜在相互作用。
F M Bianchi, G B Cavassini, P Leo

A prospective, open, multicenter clinical trial was set up to evaluate the potential interaction of ITF 282 with H2-receptor antagonists in patients affected with iron deficiency. Patients treated with H2 blockers and affected with iron deficiency or iron deficient anemia were given one tablet of ITF 282 (60 mg iron) twice daily for 60 days. A second group of iron deficient patients with no anti H2 concurrent treatment were admitted to the same iron treatment, lasting 60 days. To evaluate the outcome of the iron treatment, a comprehensive assessment of laboratory and clinical determinations was adopted in all the patients: special hematology, symptomatology, safety hematology and hematochemistry, urinalysis. Fifty-three patients with iron deficiency and 47 patients affected with overt iron deficient anemia entered the study. After treatment, a significant trend toward the normalization of the main hematologic parameters in both groups was detected. The general tolerability was apparently more favorable in the patients who had also the antiulcer (1 event of diarrhoea) than in those who had ITF 282 alone (2 heartburn, 3 constipation, 2 abdominal pain). There were no indications of subgroups of patients particularly at risk of adverse events, all of which resulted reversible without the need to reduce the dose of medication or to take other medical action. ITF 282 resulted, also when administered together with H2-receptor antagonists, in the expected therapeutic efficacy, with the expected clinical tolerability and biological safety, without signs of possible interaction, negative or positive.(ABSTRACT TRUNCATED AT 250 WORDS)

一项前瞻性、开放性、多中心临床试验旨在评估ITF 282与h2受体拮抗剂在缺铁患者中的潜在相互作用。接受H2阻滞剂治疗并伴有缺铁或缺铁性贫血的患者给予ITF 282 (60 mg铁)1片,每天2次,连续60天。第二组缺铁患者未同时接受抗H2治疗,接受相同的铁治疗,持续60天。为了评价铁治疗的效果,对所有患者的实验室和临床指标进行综合评估:特殊血液学、症状学、安全血液学和血液化学、尿液分析。53名缺铁患者和47名明显缺铁性贫血患者参加了这项研究。治疗后,两组患者的主要血液学指标均有明显的正常化趋势。与单独使用ITF 282的患者(2次胃灼热,3次便秘,2次腹痛)相比,同时使用抗溃疡药物的患者(1次腹泻)的总体耐受性明显更好。没有迹象表明亚组患者特别有不良事件风险,所有这些不良事件的结果都是可逆的,无需减少药物剂量或采取其他医疗措施。当ITF 282与h2受体拮抗剂一起使用时,结果也达到预期的治疗效果,具有预期的临床耐受性和生物学安全性,没有可能的相互作用迹象,阴性或阳性。(摘要删节250字)
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引用次数: 0
Pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy male volunteers. 治疗阿尔茨海默病的新化合物E2020在健康男性志愿者体内的药代动力学
M Mihara, A Ohnishi, Y Tomono, J Hasegawa, Y Shimamura, K Yamazaki, N Morishita

E2020 is a new cholinesterase inhibitor with a novel chemical structure, which is under clinical investigation for use in Alzheimer's disease in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E2020 after oral administration to healthy male subjects. E2020 was administered as: (1) single oral doses (0.3 mg, 1 mg, 2 mg, 5 mg, 8 mg and 10 mg) in a fasting condition, (2) a single oral dose (2 mg) after a meal and (3) repeated oral doses (2 mg once daily for 21 days). The concentrations of E2020 and its metabolites in plasma, serum, urine and feces were determined by HPLC methods with UV detection. E2020 was generally well tolerated by all subjects. In the single-dose study, there was a linear relationship between dose and mean AUC. The mean plasma half-life was about 50 hours and was dose-independent. The total clearance and renal clearance of E2020 were also dose-independent and the mean values after 10 mg dosing were 9.7 l/hour and 0.86 l/hour, respectively. The cumulative total urinary and fecal excretion of the sum of unchanged E2020 and its metabolites at 264 hours after the administration of the single 10-mg-dose was 36.1% and 8.6% of the dose, respectively. The mean serum protein binding was 92.6%. No effect of food intake on the pharmacokinetics was observed. Evaluation of the mean trough levels and AUC0-24 of E2020 indicated that a steady-state was achieved after approximately 2 weeks of daily dosing.

E2020是一种具有新型化学结构的新型胆碱酯酶抑制剂,目前正在日本和美国进行用于阿尔茨海默病的临床研究。为了评估E2020对健康男性口服后的安全性并建立其药代动力学特征,进行了三项独立的研究。E2020的给药方式为:(1)空腹单次口服剂量(0.3 mg、1 mg、2 mg、5 mg、8 mg和10 mg),(2)餐后单次口服剂量(2 mg),(3)重复口服剂量(2 mg,每天1次,连续21天)。采用高效液相色谱-紫外检测法测定血浆、血清、尿液和粪便中E2020及其代谢物的浓度。所有受试者对E2020总体耐受良好。在单剂量研究中,剂量与平均AUC呈线性关系。平均血浆半衰期约为50小时,与剂量无关。E2020的总清除率和肾清除率也与剂量无关,给药10 mg后的平均值分别为9.7 l/小时和0.86 l/小时。10 mg单次给药264小时,未改变E2020及其代谢物的累计尿排泄总量和粪便排泄总量分别为给药剂量的36.1%和8.6%。平均血清蛋白结合率为92.6%。没有观察到食物摄入量对药代动力学的影响。对E2020的平均波谷水平和AUC0-24的评估表明,每日给药约2周后达到稳定状态。
{"title":"Pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy male volunteers.","authors":"M Mihara,&nbsp;A Ohnishi,&nbsp;Y Tomono,&nbsp;J Hasegawa,&nbsp;Y Shimamura,&nbsp;K Yamazaki,&nbsp;N Morishita","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>E2020 is a new cholinesterase inhibitor with a novel chemical structure, which is under clinical investigation for use in Alzheimer's disease in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E2020 after oral administration to healthy male subjects. E2020 was administered as: (1) single oral doses (0.3 mg, 1 mg, 2 mg, 5 mg, 8 mg and 10 mg) in a fasting condition, (2) a single oral dose (2 mg) after a meal and (3) repeated oral doses (2 mg once daily for 21 days). The concentrations of E2020 and its metabolites in plasma, serum, urine and feces were determined by HPLC methods with UV detection. E2020 was generally well tolerated by all subjects. In the single-dose study, there was a linear relationship between dose and mean AUC. The mean plasma half-life was about 50 hours and was dose-independent. The total clearance and renal clearance of E2020 were also dose-independent and the mean values after 10 mg dosing were 9.7 l/hour and 0.86 l/hour, respectively. The cumulative total urinary and fecal excretion of the sum of unchanged E2020 and its metabolites at 264 hours after the administration of the single 10-mg-dose was 36.1% and 8.6% of the dose, respectively. The mean serum protein binding was 92.6%. No effect of food intake on the pharmacokinetics was observed. Evaluation of the mean trough levels and AUC0-24 of E2020 indicated that a steady-state was achieved after approximately 2 weeks of daily dosing.</p>","PeriodicalId":13817,"journal":{"name":"International journal of clinical pharmacology, therapy, and toxicology","volume":"31 5","pages":"223-9"},"PeriodicalIF":0.0,"publicationDate":"1993-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19301425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of acetylcholinesterase by distigmine bromide (Ubretid). 溴异丁胺对乙酰胆碱酯酶的抑制作用。
H P Breuel, W Bohn-Olszewsky, S J Engelsen, E M Samhaber, H Niklaus

A randomized phase-I study was performed in a clinical setting in 24 healthy young male subjects, aged 20 to 35 years, to investigate the influence of Ubretid on AChE inhibition following oral and i.m. administration in one of three medication schemes: -single oral (10 mg) and i.m. (0.5 mg) medication (randomized crossover), -multiple oral dosing (5 mg on trial days 1, 2, 3, 5, 7, 9, 11 and 13), -multiple oral dosing (5 mg on trial days 5 to 14) with initial i.m. loading doses (0.5 mg i.m. on trial days 1, 2 and 4). The multiple dosing schemes were chosen as they are both frequently used in clinical practice. The results of the AChE inhibition after Ubretid can be summarized as follows: repeated Ubretid administration as used in this trial did not lead to a cumulation of AChE inhibition. Statistical testing (page test) of maximum AChE inhibition on the last medication days gave no indication of an increased AChE inhibition towards the end of treatment. Compared with the i.m. administration, the Ubretid tablet had a bioavailability of 2.2 +/- 1.1% (mean +/- STD).

在临床环境中对24名年龄在20至35岁的健康年轻男性受试者进行了一项随机i期研究,以调查Ubretid在口服和静脉注射三种药物方案之一后对乙酰胆碱酯酶抑制的影响:-单次口服(10毫克)和点滴(0.5毫克)给药(随机交叉),-多次口服给药(试验第1、2、3、5、7、9、11和13天5毫克),-多次口服给药(试验第5至14天5毫克),初始点滴负荷剂量(试验第1、2和4天0.5毫克)。选择多重给药方案是因为它们在临床实践中经常使用。Ubretid后AChE抑制的结果可以总结如下:本试验中使用的Ubretid重复给药并未导致AChE抑制的累积。最后用药日最大AChE抑制的统计检验(page test)没有显示治疗结束时AChE抑制增加的迹象。与im给药相比,Ubretid片的生物利用度为2.2 +/- 1.1%(平均+/- STD)。
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引用次数: 0
Myeloid hemopoietic growth factors. Review article. 髓系造血生长因子。评论文章。
R Vrhovac, R Kusec, B Jaksić

The article is a critical review of recent publications on myeloid hemopoietic growth factors. They are glycoproteins that regulate the proliferation and differentiation of hemopoietic progenitor cells and the function of mature blood cells. They are also named colony stimulating factors after the experimental technique that led to their discovery. Myeloid growth factors are: granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF) and interleukin-3. Studies of hemopoietic growth factors in the past years have revealed many potential beneficial effects, but some limitations as well. They have been proved effective, above all, in neutropenic conditions of different origin. A large number of clinical trials have shown their beneficial effect in myelosuppressive conditions after cytotoxic chemotherapy, in post-transplant period in bone marrow transplantation procedures and in neutropenic conditions as part of other clinical entities. Although a number of studies that should determine their clinical role more clearly is still underway, it seems certain that myeloid hemopoietic growth factors already have an important role in modern pharmacotherapy.

这篇文章是对最近发表的髓系造血生长因子的综述。它们是调节造血祖细胞增殖和分化以及成熟血细胞功能的糖蛋白。根据发现它们的实验技术,它们也被命名为集落刺激因子。髓系生长因子有:粒细胞巨噬细胞集落刺激因子(GM-CSF)、粒细胞集落刺激因子(G-CSF)、巨噬细胞集落刺激因子(M-CSF)和白细胞介素-3。近年来对造血生长因子的研究揭示了许多潜在的有益作用,但也存在一些局限性。它们已被证明是有效的,尤其是在不同来源的中性粒细胞减少的情况下。大量的临床试验表明,在细胞毒性化疗后的骨髓抑制条件下,在骨髓移植手术后的移植期和中性粒细胞减少的条件下,作为其他临床实体的一部分,它们都有有益的作用。尽管许多研究仍在进行中,以更清楚地确定其临床作用,但似乎可以肯定的是,髓系造血生长因子在现代药物治疗中已经发挥了重要作用。
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引用次数: 0
Changes in beta-adrenergic receptors of rat heart and adipocytes during volume-overload induced cardiac hypertrophy. 容量过载诱导心肌肥厚时大鼠心脏β -肾上腺素能受体和脂肪细胞的变化。
G Cartagena, M Sapag-Hagar, J Jalil, V Tapia, E Guarda, R Foncea, R Corbalan, R Ebensperger, S Lavandero

Modification of cardiac beta-adrenergic receptors (beta-AR), resulting from the stimulation of the sympathetic nervous system, is one of the most important factors in the generation of cardiac hypertrophy and heart failure. In this research, we propose the utilization of adipocytes as an alternative to the use of predominantly beta 2-AR subtype containing circulating lymphocytes for the convenient assessment of cardiac failure in the experimentally, volume-overload induced heart hypertrophy in rats. Using this model, we measured beta-AR both in the heart and adipocytes of male rats 2, 7, 21 and 56 days after creating an aorta-cava fistula. Whereas an increase (58%) in cardiac beta-AR density from day 7 to 21 was followed by a decrease in this measurement (30%) on day 56 [changes expressed as percentage of controls; no significant changes in beta-AR affinity (Kd) were recorded at any of the time interval studied], adipocytes beta-AR density showed a progressive increase starting on day 21 (87%) which continued until the end (131%) of the study period. This lack of correlation of the beta-AR population in both tissues supports the need for a specific evaluation of the beta 1-AR subtype in the heart and adipocyte in order to evaluate the usefulness of adipocyte cells as an alternative to assess cardiac failure.

交感神经系统的刺激引起的心脏β -肾上腺素能受体(β - ar)的改变是导致心脏肥厚和心力衰竭的重要因素之一。在这项研究中,我们提出利用脂肪细胞替代主要含有β 2-AR亚型的循环淋巴细胞,以方便地评估实验性,容量过载诱导的大鼠心脏肥厚的心力衰竭。利用该模型,我们测量了雄性大鼠在主动脉-腔瘘形成后2、7、21和56天的心脏和脂肪细胞中的β - ar。然而,心脏β - ar密度从第7天到第21天增加(58%),随后在第56天减少(30%)[变化以对照组的百分比表示;在研究的任何时间间隔内均未记录到β - ar亲和力(Kd)的显著变化],脂肪细胞β - ar密度从第21天开始逐渐增加(87%),并持续到研究期结束(131%)。两种组织中β - ar群体缺乏相关性,因此需要对心脏和脂肪细胞中的β - 1-AR亚型进行特异性评估,以评估脂肪细胞作为评估心力衰竭的替代方法的有效性。
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引用次数: 0
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International journal of clinical pharmacology, therapy, and toxicology
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