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Preclinical qualitative evaluation of the antitumoral pharmacodynamic action of some natural polyphenolic biopreparations. 一些天然多酚类生物修复剂抗肿瘤药效学作用的临床前定性评价。
P Rotinberg, S Kelemen, M Gramescu, H Rotinberg, V Nuta

We have investigated the impact of POLYAS I and POLYAS II polyphenolic biopreparations - specifically separated and purified from Asclepias syriaca leaves, and characterized in vitro as cytotoxic and/or cytostatic agents - on the tumor generation process. A series of in vivo tests of their effect on the development of Guerin T-8 lymphotropic epithelioma and Walker 256 carcinosarcoma were conducted. In a first stage of preclinical trial we had used several tests meant to evaluate their antitumoural activity indices. The same tests were then used under similar experimental conditions in the solid tumoral systems mentioned. A comparative analysis of the antitumoral activity evaluation indices resulting from our tests with the reference indices set by the American and German preclinical screening programs pointed to their compatibility. Thus, we found similar values of mean tumoral regressions, of the ratio between mean tumoral weights of the treated and control groups, respectively, of the T/C products resulting from successive re-tests. Also T/C values resulting from retests were within the limits of admissible variability range. All those results highlighted the antineoplastic pharmacotherapeutic effect of the polyphenolic biopreparations and also proved that effect to be replicable. The qualitative evaluation of the pharmacodynamic action of those preparations was a condition for their further quantitative pharmacological evaluation in point of antitumoral therapeutic effectiveness in a preclinical stage.

我们研究了POLYAS I和POLYAS II多酚生物修复剂对肿瘤生成过程的影响。POLYAS I和POLYAS II多酚生物修复剂是从叙利亚芦仙叶中分离纯化的,并在体外被鉴定为细胞毒性和/或细胞抑制剂。我们进行了一系列体内试验,研究了它们对Guerin T-8淋巴细胞嗜性上皮瘤和Walker 256癌肉瘤的影响。在临床前试验的第一阶段,我们使用了几种旨在评估其抗肿瘤活性指数的测试。然后在上述实体肿瘤系统的类似实验条件下使用相同的测试。我们的试验得出的抗肿瘤活性评价指标与美国和德国临床前筛选项目设定的参考指标进行了比较分析,指出了它们的相容性。因此,我们发现了相似的平均肿瘤回归值,分别是治疗组和对照组的平均肿瘤重量之比,以及连续重新测试产生的T/C产物。此外,由复测得出的T/C值在可接受的变异性范围内。这些结果突出了多酚类生物修复剂的抗肿瘤药物治疗作用,也证明了这种作用是可复制的。对这些制剂的药效学作用进行定性评价是进一步在临床前阶段对其抗肿瘤治疗效果进行定量药理学评价的条件。
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引用次数: 0
Preliminary research on possible relationship of NO with agmatine at the vascular level. 血管水平一氧化氮与胍丁氨酸可能关系的初步研究。
I Haulică, W Bild, R Iliescu, R Georgescu, F Frunză

The comparative study of the vascular effects of agmatine and L-arginine as physiological precursors of NO indicated the following: When administered intravenously, both vasoactive substances produced a decrease of the systemic blood pressure in rats and rabbits, diminished in the case of agmatine and suppressed in that of arginine by the previous administration of L-NAME. Myorelaxing vascular effects were obtained in isolated thoracic aorta rings, precontracted with phenylephrine and noradrenaline. Endothelium removal suppressed the myorelaxing properties of L-arginine, without affecting the effects of agmatine, both before and after administration of L-NAME or yohimbine. The persistence of the relaxing effects of agmatine after NOS and guanylate-cyclase inhibition with methylene blue excludes the participation of NO and cGMP in their occurrence. The enhancement of agmatine myorelaxation by moxonidine pleads for the stimulation of imidazoline receptors.

对作为NO生理前体的胍丁氨酸和l -精氨酸的血管作用的比较研究表明:当静脉给药时,这两种血管活性物质都能降低大鼠和家兔的全身血压,胍丁氨酸的血压降低,精氨酸的血压被先前给药的L-NAME所抑制。用苯肾上腺素和去甲肾上腺素预收缩胸主动脉环,获得肌舒张血管效应。在给予L-NAME或育亨宾前后,内皮去除抑制了l -精氨酸的肌肉松弛特性,而不影响胍丁氨酸的作用。在NOS和亚甲基蓝抑制鸟苷酸环化酶后,胍丁氨酸的松弛作用持续存在,排除了NO和cGMP参与其发生。莫替尼定对胍丁氨酸肌松弛的增强是通过刺激咪唑啉受体实现的。
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引用次数: 0
Oxidative injury and other metabolic disorders in hepatic encephalopathy. 肝性脑病的氧化损伤及其他代谢紊乱。
T Negru, V Ghiea, D Păsărică

Within the complex mechanism of hepatic encephalopathy resulting from alcohol poisoning, a significant pathogenic role seems to relate to lipid peroxides (free radicals generated by chronic alcohol poisoning itself). Oxidative aggression is emphasized by the diminishing antioxidative capacity of the body resulting from serious liver injury brought about by chronic ethyl poisoning. The poisoning influences the whole functional capacity of the liver, hepatic protein synthesis included, which also means ceruloplasmin and siderophilin synthesis; the two latter elements make up AOS Cp-Tr which neutralizes the harmful activity of Cu and Fe excess and stimulates release of free radicals of oxygen. The purpose of our research was to study the redox balance alteration in blood in a group of patients who were in a critical condition and had been admitted to the somatic patients ward of the "Prof. Dr. Alexandru Obregia" Neurology and Psychiatry Hospital and who were suffering from hepatic encephalopathy resulting from ethyl poisoning.

在酒精中毒引起的肝性脑病的复杂机制中,脂质过氧化物(慢性酒精中毒本身产生的自由基)似乎起着重要的致病作用。慢性乙基中毒引起严重肝损伤,机体的抗氧化能力下降,强调了氧化攻击。中毒影响肝脏的整体功能,包括肝蛋白的合成,也包括铜蓝蛋白和嗜铁蛋白的合成;后两种元素构成AOS Cp-Tr,它中和过量的Cu和Fe的有害活性,并刺激氧自由基的释放。我们的研究目的是研究一组因乙基中毒而患肝性脑病的危重病人的血液氧化还原平衡变化,这些病人曾住进“Alexandru博士”神经病学和精神病学医院的躯体病人病房。
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引用次数: 0
Experimental studies concerning the possible involvement of adenosine in maintaining the hydroelectrolytic balance. 关于腺苷可能参与维持水电解质平衡的实验研究。
S M Slătinean, M Costuleanu, I Mândreci, G Petrescu

The study focused on the effects of intracerebroventricular (i.c.v.) administration of adenosine (10(-7)-10(-5) M) on water metabolism and some electrolytes in adults rats. The i.c.v. administered adenosine decreases both spontaneous and angiotensin II (Ang II) induced ingestion of sodium chloride solution (9/1000). Urinary release was differently influenced. Thus, while the released urinary volume increased in the first 4 hours after adenosine injection, it was not significantly modified on successive administration of adenosine and Ang II. Adenosine decreases the urinary releases of Na+ and K+ and dramatically reduces only Ang II-induced natriuresis. Finally, we can conclude that neural chains involved in the control of uptake and release of water and some ions, include neurons and/or purinergic interneurons.

本研究主要研究了脑室灌注腺苷(10(-7)-10(-5)M)对成年大鼠水代谢和部分电解质的影响。静脉滴注腺苷可降低氯化钠溶液自发摄入和血管紧张素II (Ang II)诱导摄入(9/1000)。尿释放受到不同程度的影响。因此,虽然在注射腺苷后的前4小时内尿量释放量增加,但连续给药腺苷和Ang II后尿量没有明显改变。腺苷减少尿中Na+和K+的释放,并显著减少Ang ii诱导的尿钠。最后,我们可以得出结论,参与控制水和某些离子的摄取和释放的神经链包括神经元和/或嘌呤能中间神经元。
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引用次数: 0
Thymo-adrenals reaction in pre-pubertal and pubertal Wistar rats in response to acute administration of calcitonin. 青春期前和青春期Wistar大鼠对降钙素急性给予的胸腺-肾上腺反应。
R Giurgea, I Roman, D Borda, D Pop

Pre- and post-pubertal Wistar rats were injected i.m. with a single dose equivalent to 1 UI of Calcitonin (Calsyn-50 Rorer, Swiss). Its effects upon the thymus and adrenals were assessed after 1, 3 and respectively, 8 days since injection. The results pointed to differences of reaction of the thymus and adrenals dependent on rat ages and on the period of hormone persistence in the organism. The effects in mature rats are characterized by a stress state, reflected in adrenal reaction, but without impact upon the thymus in point of biochemical parameters. In rats of that age, modifications in both organs are much reduced after 8 days since calcitonin injection. In pubertal rats, adrenal activity is temperate, and thymus registers modification of DNA, of oxygen consumption and of nitrogen aminic after 3 days since injection. This modification is maintained for 8 days.

将青春期前和青春期后的Wistar大鼠单次注射相当于1ui的降钙素(calsyn50 Rorer, Swiss)。分别于注射后1、3、8天观察其对胸腺和肾上腺的影响。结果表明,胸腺和肾上腺的反应随大鼠年龄和激素持续时间的不同而不同。对成熟大鼠的作用表现为应激状态,表现为肾上腺反应,但在生化指标上对胸腺无影响。在该年龄的大鼠中,注射降钙素8天后,两个器官的变化都大大减少。在青春期大鼠,肾上腺活动是有节制的,注射后3天胸腺记录了DNA、耗氧量和氮胺的改变。此修改维护8天。
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引用次数: 0
Thyroxin and thiouracyl influence upon some biochemical parameters in chicken thymuses. 甲状腺素和硫氧酰基对鸡胸腺某些生化指标的影响。
I Roman, R Giurgea

Administration of L-thyroxin in a dose of 30 micrograms/chicken, i.m. and 2-thiouracyl in a dose of 0.3 mg/chicken, i.m. for an interval of 3 days, determined, at the thymus level, increases of total protein content in the Tu group, in parallel with decreases of the nitrogen of free amino acids level in the Tx group, increases of DNA content in the Tx group and an increase of the thymus weight in both groups. Modifications are due to the action of thyroxin, on the one hand, and on the other to the doses of antithyroid drug which determines a raise of T4 content in the plasma and the manifestation of activities specific to this hormone.

l -甲状腺素(30微克/只,每日1次)和2-硫氧酰基(0.3毫克/只,每日1次,间隔3天)在胸腺水平上,屠组总蛋白含量升高,同时Tx组游离氨基酸氮含量降低,Tx组DNA含量升高,两组胸腺重量均增加。这种改变一方面是由于甲状腺素的作用,另一方面是由于抗甲状腺药物的剂量决定了血浆中T4含量的升高和这种激素特异性活动的表现。
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引用次数: 0
Acetylcholine constrictor effect enhanced by hydrogen peroxide in ovalbumin-sensitised rat tracheal muscle. 过氧化氢对卵清蛋白致敏大鼠气管肌乙酰胆碱收缩作用增强。
C Mederle, F Schneider

Ten Sprague-Dawley male rats were sensitised with ovalbumin. The effect of hydrogen peroxide on the constrictor effect of acetylcholine was studied in the isolated tracheal muscle. Preincubation with hydrogen peroxide (H2O2) 10(-3) M (1 min/30 min) does not modify the acetylcholine constrictor effect in the control group. Ovalbumin sensitisation enhanced the acetylcholine constrictor effect (mean value of 19%) irrespective of dosage, comparatively with the control group. Short- and long-term preincubation with hydrogen peroxide enhanced the acetylcholine effect in the sensitised group, irrespective of dosage, comparatively with the control group. A relationship between dosage, contractile response and time of incubation was noticed only in the sensitised group.

10只Sprague-Dawley雄性大鼠用卵清蛋白致敏。在离体气管肌肉中研究了过氧化氢对乙酰胆碱收缩作用的影响。在对照组中,过氧化氢(H2O2) 10(-3) M (1 min/30 min)预孵育不改变乙酰胆碱收缩效应。与对照组相比,卵清蛋白致敏增强了乙酰胆碱收缩效应(平均值19%),与剂量无关。与对照组相比,不论剂量如何,短期和长期过氧化氢预孵育均增强了敏化组的乙酰胆碱作用。剂量、收缩反应和孵育时间之间的关系仅在敏感组被注意到。
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引用次数: 0
Influence of acceleration over the hydroelectrolytic homeostasis in audiogenic seizure-prone rats compared to normoexcitable rats. 与正常兴奋大鼠相比,加速度对听原性癫痫易发大鼠水电解质稳态的影响。
M Uluitu, R Chiş, M Iftincă

This research concentrated on the hydroelectrolytic balance response after centrifugation (+5G/30 minutes, five times) in two lots of rats: one lot made up of animals with normal cerebral excitability, and another one of animals prone to audiogenic seizure. Both before and after centrifugation, we determined: water (ml/24 hrs.) and sodium chloride (mEq/24 hrs.) consumption; dependence of sodium, potassium and water elimination on the amount of sodium ingested (mEq/24 hrs.). We also determined the renal capacity of sodium concentration and the mineral-corticoid response based on the urine Na/K ratio and on the determination of plasma renin activity (PRA). Data obtained show that audiogenic seizure-prone rats consume less sodium and water after centrifugation, unlike normoexcitable rats in which there have been no differences in this respect. Exposure to hypergravitation induces in both lots an increase of sodium, potassium and water elimination. Renal elimination of water is greater in the normoexcitable animals than in the seizure-prone ones. By contrast, sodium elimination is greater in the audiogenic seizure-prone animals. Urine sodium concentration is lower in the seizure-prone animals, consistent with the amounts of water eliminated. Their mineral-corticoid response is intensely diminished after centrifugation in comparison to that of the control, normo-excitable animals. PRA is diminished in both lots. Our findings support the assumption that seizure-prone rats are unable to adaptatively respond to acceleration by preserving sodium through the intervention of cortico-surrenal mechanisms. As water is not preserved, it seems that in this category of animals, both during and after centrifugation, it is mostly the hypothalamo-retrohypophyseal mechanisms that come into play. This could be the outcome of disturbances occurring in the mechanisms of blood sodium transport that are deficient in the seizure-prone animals.

本研究集中研究了两组大鼠离心(+5G/30分钟,5次)后的水电解质平衡反应:一组为正常脑兴奋性动物,另一组为听源性癫痫易感动物。离心前后测定:水(ml/24小时)和氯化钠(mEq/24小时)消耗量;钠、钾和水的消除与钠摄取量的关系(mEq/24小时)。我们还根据尿Na/K比值和血浆肾素活性(PRA)测定了钠浓度的肾容量和矿物皮质激素反应。获得的数据表明,离心后易发生听源性癫痫发作的大鼠消耗更少的钠和水,不像正常兴奋的大鼠在这方面没有差异。暴露在超重力环境下,两组小鼠的钠、钾和水分消除量均增加。正常兴奋动物的肾脏排水量大于易发作动物。相比之下,钠的消除在听原性癫痫易发的动物中更大。易发作动物的尿钠浓度较低,与排水量一致。与正常兴奋的对照动物相比,离心后它们的矿物皮质激素反应强烈减弱。两个批次的PRA均减少。我们的研究结果支持这样的假设,即癫痫易发大鼠无法通过皮质-肾机制的干预来保存钠,从而对加速做出适应性反应。由于水没有被保存,在这类动物中,无论是在离心过程中还是在离心后,似乎主要是下丘脑-垂体后叶机制起作用。这可能是癫痫易发动物的血钠运输机制出现紊乱的结果。
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引用次数: 0
Influence of lithium on the cellular environment. 锂对细胞环境的影响。
M Uluitu, G Zamfirescu, D Uluitu, N J Birch, V S Gallicchio

In order to study the influence of lithium on the cellular environment, we conducted research in multiple experimental models: groups of rats with normal cerebral excitability and groups susceptible to audiogenic convulsion, rat neuroglia cultures and perfusion of dog isolated head. We assumed blood composition to be a good indicator of cell environment composition. Blood serotonin level differs in the two groups of animals. Lithium induces a decrease of blood serotonin and an increase of amine concentration in some of the cerebral regions of rats susceptible to audiogenic convulsions. Inverse effects occur in rats with normal cerebral excitability. In the perfused, isolated head of a dog, lithium immediately decreases blood serotonin level. Na and water have a diminished metabolization during the first 24 hrs. in both animal groups. Decrease in metabolization is somewhat greater in hyperexcitable animals. Within 48 hrs. after lithium injection, there is an increase of Na metabolization, probably determined by its storage in the interstice. Renal elimination of K decreases under the influence of lithium 48 hrs. after administering one dose of lithium. Lithium induces, immediately after injection, a decrease of blood Na concentration in the efferent flow of the jugular vein of a perfused dog head. When used in cell cultures, lithium (2 mM concentration) stimulates glial cells division (astrocytes, oligodendrocytes), increases their growth and aging rates. The effects of lithium may be due to its toxicity. Therefore, lithium alters the composition of the cellular environment depending on dose and on the state of the body.

为了研究锂对细胞环境的影响,我们在多个实验模型中进行了研究:正常脑兴奋性大鼠组和听源性惊厥易感组,大鼠神经胶质细胞培养和狗离体头部灌注。我们假设血液成分是细胞环境组成的一个很好的指标。两组动物的血清素水平不同。锂能降低大鼠的血血清素水平,并在某些容易发生听源性惊厥的大脑区域增加胺的浓度。在大脑兴奋性正常的大鼠中出现相反的效应。在灌注的、分离的狗的头部中,锂会立即降低血液中的血清素水平。钠和水在24小时内代谢减少。在两个动物群体中。过度兴奋动物的代谢减少程度更大。48小时内。注射锂后,钠代谢增加,可能与钠在间隙中的储存有关。在锂离子48小时的影响下,肾脏K的消除减少。服用一剂锂后。注射后立即引起灌注狗头颈静脉传出血流血钠浓度降低。当用于细胞培养时,锂(2毫米浓度)刺激胶质细胞分裂(星形胶质细胞,少突胶质细胞),增加其生长和衰老速度。锂的影响可能是由于它的毒性。因此,锂会根据剂量和身体状态改变细胞环境的组成。
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引用次数: 0
Hepatic artery hemodynamics in acute viral hepatitis. 急性病毒性肝炎的肝动脉血流动力学。
C Bohotin, V Leca, V Luca, M Costuleanu, M Vornicu, V Bohotin, M Bădescu

In order to evaluate the effect of the acute viral hepatitis on arterial blood flow we performed duplex Doppler US on 30 patients with acute viral hepatitis (AVH) and compared the results with those obtained on 20 normal volunteers. Hepatic artery flow (HAF) was significantly increased with the patients suffering from acute viral hepatitis. The data obtained show that the increase of arterial blood flow is not always associated with the increase of arterial velocities. We could put in evidence the presence of the hepatic artery response to altered portal blood flow (arterial buffer) during a AVH. If the increase of HAF is absolutely necessary for recovery from hepatitis, excessive increase of HAF seems to increase the time of recovery. In our study, the evolution of acute viral hepatitis was good when the HAF values did not exceed 65% of liver supply. The increase of arterial blood flow over 65% seems to limit the portal supply of the liver and in this way the amounts of regenerating substances which bathe the liver cells. The HAF value plays an important role in acute viral hepatitis evolution, so that the exploration of HAF and hepatic artery velocities may be a reliable examination in order to monitor the evolution of this disease.

为了评价急性病毒性肝炎对动脉血流的影响,我们对30例急性病毒性肝炎(AVH)患者进行了双多普勒超声检查,并与20例正常人的结果进行了比较。急性病毒性肝炎患者肝动脉血流(HAF)明显增高。所获得的数据表明,动脉血流量的增加并不总是与动脉速度的增加有关。我们可以证明肝动脉对AVH期间门静脉血流改变(动脉缓冲)的反应。如果增加HAF对于肝炎的恢复是绝对必要的,那么过度增加HAF似乎会增加恢复的时间。在我们的研究中,当HAF值不超过肝供应的65%时,急性病毒性肝炎的演变良好。动脉血流量增加超过65%似乎限制了肝脏的门静脉供应,从而限制了肝细胞再生物质的数量。HAF值在急性病毒性肝炎的演变过程中起着重要的作用,因此探测HAF和肝动脉流速可能是一种可靠的检查方法,以监测该病的演变。
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引用次数: 0
期刊
Romanian journal of physiology : physiological sciences
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