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The interaction between the cholinergic and dopaminergic system in learning and memory process in rats. 大鼠学习记忆过程中胆碱能与多巴胺能系统的相互作用。
V Hefco, K Yamada, Andreea Hefco, L Hritcu, A Tiron, T Nabeshima

In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating role on both short-term and long-term memory tested by Y-maze task and multi-trial passive avoidance test, respectively, since scopolamine, a specific mAChRs antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w., i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist, administered once caused a significant facilitating effect on short-term memory. A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days had about the same facilitating effect on short- and long-term memory without affecting information acquisition. In rats, having mAChRs and nAChRs blocked by means of scopolamine and chlorisondamine respectively, a low dose of nicotine administered once caused a significant improvement of long-term memory deficits without affecting significantly short-term memory. A higher dose of nicotine administered 5 consecutive days in rats with a double blockade of cholinergic receptors had the same ameliorating effect on long-term memory deficits as low dose. Our data suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.

在正常大鼠中,毒毒碱乙酰胆碱受体(machr)分别对y迷宫任务和多试验被动回避测试中的短期和长期记忆有促进作用,因为特异性的machr拮抗剂东莨菪碱会损害这两种类型的记忆。低剂量尼古丁(0.3 mg/kg b.w, i.p.),一种特定的尼古丁乙酰胆碱受体(nAChRs)激动剂,一次给予对短期记忆有显著的促进作用。连续5天给予高剂量尼古丁(3 mg/kg b.w., i.p.)对短期和长期记忆的促进作用大致相同,但不影响信息获取。在大鼠中,分别通过东莨菪碱和氯异旦胺阻断machr和nachr,一次给予低剂量尼古丁可显著改善长期记忆缺陷,而不显著影响短期记忆。对双胆碱能受体阻断的大鼠连续5天给予高剂量尼古丁,对长期记忆缺陷的改善效果与低剂量相同。我们的数据表明,尼古丁的抗遗忘作用可能是由于不被氯异旦胺或非尼古丁受体阻断的尼古丁受体亚型的作用。
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引用次数: 0
Modification of the muscular contractility of the vena porta in trypsinemia. 胰蛋白酶血症中门静脉肌肉收缩性的改变。
A Saulea, V Ojog

The purpose of the present work was to investigate the changes of spontaneous and induced contractility in the rat vena porta, in conditions of acute pancreatitis, artificial trypsinemia and direct action of trypsin. The amplitude, frequency and mainly the intensity of the structure functioning decrease significantly under the influence of proteolitic enzymes (trypsin). The contractility of the isolated portal vein decrease in reply of the increase or decrease of the concentration of Ca2+ ions. Thus the possible action mechanism of proteolitic enzymes action consists in damaging at the sarcolemma, which causes the decrease in the influx of Ca2+ ions during the action potential.

本研究旨在探讨急性胰腺炎、人工胰蛋白酶血症和胰蛋白酶直接作用下大鼠门静脉自发和诱导收缩力的变化。在蛋白质水解酶(胰蛋白酶)的影响下,结构功能的幅度、频率和强度显著降低。离体门静脉收缩力随Ca2+浓度的升高或降低而降低。因此,蛋白水解酶作用的可能作用机制在于破坏肌膜,导致动作电位期间Ca2+离子内流减少。
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引用次数: 0
New technical approaches in stereotaxic catheterization of cerebral ventriculi: implications for the L-arginine/NO synthase/nitric oxide cascade. 脑室立体定向置管的新技术途径:对l -精氨酸/NO合成酶/一氧化氮级联的影响。
G Manolidis, C Neamţu, D Vasincu, Irina-Maria Jaba, Oana Rădăşanu, O C Mungiu

In order to study the actions of certain substances at cerebral level, a stereotactic device for ensuring a precise catheterization of points in certain cerebral areas was used. For the operation technique was used a stereotaxic atlas specifically designed for rat brain (G. Paxinos, C. Watson, 1998), which offers all the necessary information for the identification of the trepanation. Stereotaxic implantation of cannules in the brain is useful for microinjecting solutions containing various substances (in amounts of microl), directly and targeted in the anatomical structures of the brain. The technique described can use either metalic or silastic cannules, that have variable lumen (usually for adapting a Hamilton syringe). The cannules can be implanted at cerebroventricular level, having the possibility to target all the cerebral ventricles. The intracerebroventricular (icv) administration of L-arginine induces a significant increase of response latency for mechano-algesic test. The most obvious changes are induced following the administration of the association of L-NAME with L-arginine, situation when is manifested an important increase of the response latency, starting with 5 minutes post-administration and continuing up to 45 minutes determination. The increase is significantly higher compared with the results obtained with L-arginine alone. A similar evolution is registered in the case of the plantar test.

为了研究某些物质在大脑水平上的作用,使用了一种立体定向装置,以确保对大脑某些区域的点进行精确的导管置入。手术技术采用了专门为大鼠脑设计的立体定位图谱(G. Paxinos, C. Watson, 1998),该图谱提供了识别钻孔的所有必要信息。脑内立体定向植入可用于微注射含有各种物质的溶液(以微滴为单位),直接和靶向于脑的解剖结构。所描述的技术可以使用具有可变管腔的金属或弹性管(通常用于适应汉密尔顿注射器)。套管可以在脑室水平植入,有可能靶向所有脑室。脑室内(icv)给药l -精氨酸可显著增加机械镇痛试验的反应潜伏期。最明显的变化发生在L-NAME与l -精氨酸联合给药后,反应潜伏期显著增加,从给药后5分钟开始,一直持续到45分钟。与单独使用l -精氨酸获得的结果相比,增加明显更高。足底测试的情况也有类似的演变。
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引用次数: 0
Study of the cerebral vascular Doppler velocimetry and EEG in a group of 18 cases of Alzheimer's disease. 18例阿尔茨海默病脑血管多普勒测速和脑电图的研究。
Simona I Gusti, Mugurel I Coteanu, Alice S Gusti

The authors studied the cerebral irrigation on a group of 18 patients with Alzheimer disease (60-70 year old) using the Doppler (D) ultrasound vascular method and EEG. They used a type UDP-10 Sonopan, with a sound acquisition system and graphic of recording on a 6 NEK-4 polyrecorder for registration of the carotid D curves together with ECG and phonocardiogram. EEG was registered using a Bioscript 2000. The statistical analysis of the D curves parameters for a group of 18 patients, compared to the parameters of a group of 40 clinically healthy persons, showed a decrease of the systolic speed with 24% and of the diastolic speed with 11%, a delay of the flow with the systolic spike in plateau and a murmur at the carotid arteries in 33% of the patients. These modifications point to the reduction of the cerebral vascular filling, determined especially by the atherosclerosis process which causes important narrowing of the vascular lumen but probably determined by Alzheimer disease also. We remarked the presence of theta waves in 42% of the patients and a small correlation (r = 0.38) with the decrease of the systolic speed in the test group.

作者采用多普勒超声血管法和脑电图对18例60 ~ 70岁阿尔茨海默病患者进行脑灌洗研究。他们使用UDP-10型Sonopan,配有声音采集系统和6 NEK-4多路记录仪上的记录图形,用于记录颈动脉D曲线以及心电图和心音图。脑电图是用Bioscript 2000登记的。对18例患者的D曲线参数进行统计分析,与40例临床健康人的D曲线参数进行比较,结果显示,其中33%的患者收缩速度下降24%,舒张速度下降11%,血流延迟伴收缩期平台尖峰,颈动脉有低音。这些变化表明脑血管充盈的减少,特别是由动脉粥样硬化过程决定的,动脉粥样硬化过程导致血管腔的重要变窄,但可能也由阿尔茨海默病决定。我们注意到42%的患者存在θ波,并且与实验组收缩速度的降低有很小的相关性(r = 0.38)。
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引用次数: 0
The relationship between respiratory sinus arrhythmia and heart rate during anesthesia in rat. 麻醉大鼠呼吸窦性心律失常与心率的关系。
M Moldovan, S Spulber, V Saravan, R Iosifescu, Ana-Maria Zăgrean, L Zăgrean

During inspiration the heart rate (HR) increases and during expiration it decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous heart rate variability (HRV) can be measured as the high frequency (HF) component of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of HR is associated with an increase in HF. The aim of this study was to investigate whether this relationship between HF and HR is preserved during anesthesia in rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to investigate the effect of atropine (N=3), against controls (N=3). Short term HRV was investigated in 30 seconds long epochs. HF was considered the frequency band between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the HF. Respiratory frequency (RF) was quantified as the mean spectral frequency within the HF band. One minute estimates of HR, RSA and HF were calculated by averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3 bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that: (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in HR; (3) the time-dependent increase in RSA is preserved after atropine. We conclude that the correlation between RSA and HR reflects the cardio-pulmonary coupling under parasympathetic control.

吸气时心率(HR)增加,呼气时心率降低。呼吸性窦性心律失常(RSA)对自发性心率变异性(HRV)的贡献可以通过心电图连续R-R间期变化的高频分量来衡量。在意识清醒的大鼠中,HR的减慢与HF的增加有关。本研究旨在探讨大鼠麻醉过程中HF和HR之间的这种关系是否保留。记录15只大鼠(N=15)在中度水合氯醛(CHL)麻醉下15分钟长的心电信号。记录时间延长45分钟,观察阿托品(N=3)对对照组(N=3)的影响。短期HRV在30秒长的时间内被调查。HF被认为是0.8到1.6 Hz之间的频段。RSA被量化为HF的相对谱功率。呼吸频率(RF)量化为高频频带内的平均频谱频率。HR, RSA和HF的1分钟估计值是通过平均3个30秒重叠50%来计算的。平均心率为427 +/- 3 bpm。当转速为71 +/- 1 rpm时,RSA值为45 +/- 1%。我们发现:(1)CHL麻醉大鼠HR降低与RSA升高相关;(2)阿托品降低了RSA和HR的时间依赖性降低;(3)使用阿托品后,RSA随时间的增加保持不变。我们得出结论,RSA和HR之间的相关性反映了副交感神经控制下的心肺耦合。
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引用次数: 0
Are polyamines involved in the contractile effects of angiotensin II in the rat aorta? (Polyamines and angiotensin II in rat aorta). 多胺是否参与大鼠主动脉血管紧张素II的收缩作用?(大鼠主动脉多胺和血管紧张素II)。
Natalia Costuleanu, Liliana Foia, Simona Mihaela Slătineanu, M Costuleanu, G Petrescu

Angiotensin II (AII) is a central factor involved in the pathophysiology of arterial hypertension and atherosclerosis. On the other hand, polyamines represent a family of organic cations with low molecular weight, playing intracellular regulatory roles essential for the cellular growth and differentiation. The cellular contents, the synthesis and the transport of polyamines are increased following the actions of AII, as well as of other cellular growth factors. Our results show that the administration of polyamines as pre-treatment modulates the contractile effects of extracellular AII (80 nM). This modulation is concentration-dependent and dual: the lower concentrations amplify and the higher concentrations reduce the effects of AII in the isolated rat aorta rings without endothelium. Moreover, DL-alpha-Difluoromethylomithine (DFMO), a specific inhibitor of ornithine decarboxylase, does not significantly modify the contractile effects of AII. Thus, these data suggest that polyamines generated through this metabolic pathway are not involved in the contractile effects of AII in rat aortic vascular smooth muscle.

血管紧张素II (AII)是参与动脉高血压和动脉粥样硬化病理生理的核心因子。另一方面,多胺是一类低分子量的有机阳离子,在细胞生长和分化中起着重要的细胞内调节作用。AII和其他细胞生长因子的作用增加了细胞内多胺的含量、合成和转运。我们的研究结果表明,多胺作为预处理可以调节细胞外AII (80 nM)的收缩作用。这种调节是浓度依赖性的和双重的:在没有内皮的离体大鼠主动脉环中,低浓度会增强AII的作用,而高浓度会减弱AII的作用。此外,dl - α -二氟甲基亚胺(DFMO)是鸟氨酸脱羧酶的特异性抑制剂,不会显著改变AII的收缩作用。因此,这些数据表明,通过这种代谢途径产生的多胺不参与AII在大鼠主动脉血管平滑肌中的收缩作用。
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引用次数: 0
Motor cortex plasticity--from physiology to clinical neurology. 运动皮层可塑性——从生理学到临床神经学。
Cătălina Roxana Bohotin, Magda Bădescu, D N Popescu, V Bohotin

Neurophysiologic, neuroanatomic and neuroimaging studies conducted over the past two decades reveal that the cerebral cortex is functionally and structurally dynamic. The functional topography of the motor cortex can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmocologic treatment or behavioral experience. Recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. This article describes the state of the science regarding the main mechanisms implicated in the motor cortex plasticity, the main tools used for its investigation and the consequence of the recent discoveries on the therapeutic and rehabilitation procedures for the brain-injured persons.

过去二十年的神经生理学、神经解剖学和神经影像学研究表明,大脑皮层在功能和结构上是动态的。运动皮层的功能地形可以通过各种实验操作来改变,包括外周或中枢损伤、电刺激、药物治疗或行为体验。最近的证据表明,运动皮层组织的功能改变伴随着树突和突触结构的改变,以及皮层神经递质系统调节的改变。本文介绍了运动皮质可塑性的主要机制的科学现状,用于其研究的主要工具,以及最近在脑损伤患者的治疗和康复过程中的发现。
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引用次数: 0
Pathogenic pathways in acute myeloid leukemias. 急性髓性白血病的致病途径。
A Cucuianu

Despite the common clinical, hematological and prognostic features that define acute myeloid leukemia (AML) there is considerable heterogeneity among individual cases, suggesting different pathogenic pathways. Based on a simple theoretical model, according to the vital characteristics of the leukemic clone (proliferative rate and resistance to apoptosis) we propose a classification of AML into two broad categories: a) high leukemic clone vitality (HLV) AML, corresponding roughly to the World Health Organization (WHO) classification group of entities "AML with recurrent cytogenetic abnormalities" and b) low leukemic clone vitality (LLV) or "opportunistic" AML corresponding to the WHO groups "AML with multilineage dysplasia" and "therapy-related AML". HLV-AML leukemic clones are characterized by rate-limiting genomic mutations capable of conferring proliferation/survival advantage over a normal hematopoietic environment while in LLV-AML, the leukemic clones are not particularly proliferative or apoptosis-resistant, but are nevertheless selected against an impaired, previously damaged hematopoietic environment. Such a pathogenesis-oriented classification might have therapeutic and prognostic implications, providing a theoretical basis for a further adaptation of the current standard treatment strategies to the individual characteristics of the AML patients.

尽管急性髓性白血病(AML)具有共同的临床、血液学和预后特征,但在个体病例中存在相当大的异质性,表明不同的致病途径。基于一个简单的理论模型,根据白血病克隆的重要特征(增殖率和对细胞凋亡的抵抗),我们将AML分为两大类:a)高白血病克隆活力(HLV) AML,大致相当于世界卫生组织(WHO)分类组的实体“AML伴复发性细胞遗传学异常”,b)低白血病克隆活力(LLV)或“机会性”AML,相当于WHO分类组的“AML伴多系不典型增生”和“治疗相关性AML”。HLV-AML白血病克隆的特点是具有速率限制的基因组突变,能够在正常的造血环境中赋予增殖/生存优势,而LLV-AML白血病克隆并不是特别具有增殖性或抗凋亡性,但仍然是针对受损的、先前受损的造血环境进行选择的。这种以发病机制为导向的分类可能具有治疗和预后意义,为进一步调整当前标准治疗策略以适应AML患者的个体特征提供理论依据。
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引用次数: 0
Experimental data regarding the implications of certain minimum structure enkephalin-like peptides in nociceptive processing. 某些最小结构脑啡肽样肽在伤害性加工中的意义的实验数据。
Irina M Jaba, D Vasincu, G Manolidis, I Haulică, O C Mungiu

The aim of this study was to investigate the importance of the amino acidic sequence at N-terminal end of certain minimum structure enkephalin-like peptides for the analgesic activity. Different groups of mice or rats were treated with 1) L-tyrosine (i.p. 200 mg/kg), 2) Tyr-Phe (i.t. 0.5 mg/rat), 3) Tyr-Pro-Phe (i.t. 0.5 mg/rat), 4) Gly-Tyr (i.t. 0.5 mg/rat), 5) Tyr-Gly-Gly (i.t. 0.5 mg/rat). Different tests were utilized to evaluate the antinociceptive effect of the substances tested: thermal nociception (hot plate test, plantar test), mechanical nociception (analgesymeter test). Tyr-Pro-Phe, Tyr-Gly-Gly, Tyr-Phe, but not Gly-Tyr, elicited analgesic activity. So, the presumption made in the case of atypical opioid peptides that opioid-like activity in case of peptides presumes a tyrosine residue at the N-terminal sequence, applies for shorter peptides. It appears also that minimal structure brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opioids, can provide better affinity for the opioid receptors and stronger analgesic activity. The inhibition of their analgesic effect by previous administration of naloxone proves that this effect is mediated through the endogenous opioid system.

本研究的目的是探讨某些最小结构脑啡肽样肽n端氨基酸序列对镇痛活性的重要性。各组小鼠或大鼠分别给予1)l -酪氨酸(灌胃200 mg/kg)、2)酪氨酸-丙氨酸(灌胃0.5 mg/kg)、3)酪氨酸-脯氨酸(灌胃0.5 mg/kg)、4)甘氨酸-酪氨酸(灌胃0.5 mg/kg)、5)甘氨酸-甘氨酸-甘氨酸(灌胃0.5 mg/kg)。采用热痛觉(热板试验、足底试验)、机械痛觉(镇痛计试验)两种不同的试验来评价所测物质的抗痛觉作用。Tyr-Pro-Phe, Tyr-Gly-Gly, Tyr-Phe,但Gly-Tyr不具有镇痛活性。因此,在非典型阿片样肽的情况下,阿片样活性在肽的情况下假定在n端序列有酪氨酸残基,适用于较短的肽。与其他内源性阿片的典型的Tyr-Gly-Gly-Phe序列相比,具有n端Tyr-Pro序列的最小结构脑肽对阿片受体具有更好的亲和力和更强的镇痛活性。先前服用纳洛酮对其镇痛作用的抑制证明这种作用是通过内源性阿片系统介导的。
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引用次数: 0
Modelling of ion permeation in K+ channels by nonequilibrium molecular dynamics simulations: I. Permeation energetics and structure stability. 离子在K+通道中渗透的非平衡分子动力学模拟:1 .渗透能量学和结构稳定性。
A Neamţu, Daniela Suciu

Because of the great importance of physiological and pathophysiological processes in which ion channels are involved and because their operation is described by physicochemical laws, there have been many attempts to develop physical models able to describe the membrane permeability and also the structural and functional properties of the channel protein structures. In this study (in two parts) we present a series of simulations on a K+ channel model (KcsA) using Nonequilibrium Molecular Dynamics simulations (NEMD), in order to follow structure stability, permeation energetics and the possibility of obtaining quantitative information about the permeation process using the Linear Response Theory (LRT). On K+ ions were applied external forces to determine them to pass through the channel in a relatively small amount of time, accessible computationally. We ascertained a high resistance of the protein to deformation even in conditions when great forces were applied on ions (the system was far from equilibrium). The estimation of energy profiles in the course of ions passage through the channel demonstrates that these proteins create a conductivity pathway with no energetic barriers for ions movement across the channel (which could be present due to ions dehydration). The dynamic model used demonstrates (as proposed before in the literature after the examination of the static KcsA structure obtained by X-Ray crystallography) that this is due to the interaction of ions with the negatively charged carbonyl oxygens of the main polypeptide chain in the selectivity filter region.

由于离子通道所涉及的生理和病理生理过程的重要性,以及它们的运作是由物理化学定律描述的,人们已经尝试建立能够描述膜通透性以及通道蛋白结构和功能特性的物理模型。在本研究(分两部分)中,我们利用非平衡分子动力学模拟(NEMD)对K+通道模型(KcsA)进行了一系列模拟,以跟踪结构稳定性、渗透能量学以及利用线性响应理论(LRT)获得渗透过程定量信息的可能性。在K+离子上施加外力,以确定它们在相对较短的时间内通过通道,可计算。我们确定了即使在离子上施加很大的力的情况下,蛋白质也具有很高的抗变形能力(系统远未达到平衡)。离子通过通道过程中能量分布的估计表明,这些蛋白质创造了一个电导率途径,没有离子穿过通道的能量障碍(这可能是由于离子脱水造成的)。所使用的动态模型表明(正如之前在文献中提出的那样,在检查了x射线晶体学获得的静态KcsA结构后),这是由于离子与选择性过滤区域主多肽链上带负电的羰基氧的相互作用。
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引用次数: 0
期刊
Romanian journal of physiology : physiological sciences
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