In vivo receptor binding,neurochemical and functional studies with the dopamine D-1 receptor antagonist SCH 23390

Summary A series of in vivo experiments were undertaken, relating functional (motor activity, body temperature), dopamine (DA) receptor binding and neurochemical (catecholamine synthesis and utilization, DA release) aspects of the pharmacology of SCH 23390 in the rat.The compound inhibited the locomotor hyperactivity, but not the hypothermia, induced by the potent DA stimulant DP-5,6-ADTN. Interstingly, SCH 23390 simultaneously failed to displace DP-5,6-ADTN from its binding sites in the rat striatum—used as a direct in vivo biochemical index of DA (D-2) receptor interaction. The spontaneous locomotion in non-pretreated rats was likewise inhibited by SCH 23390. The locomotor-suppressive action, but not the DP-5,6-ADTN-displacing capcity of the D-2 blocker haloperidol was significantly enhanced by SCH 23390, suggesting that motility can be suppressed by either enhanced D-1 or D-2 (postsynaptic) receptor blockade, but also that the D-1 and D-2 sites involved may be physically distinct.SCH 23390 only slightly altered in vivo neurochemical of DA synthesis, release and nerve-impulse flow, indicating that, while similar in suppressing dopaminergic behaviour, the D-1 antagonist is less effective than traditional neuroleptics as an activator of DA neuronal feedback mechanisms. The weak increases of DA synthesis and release nonetheless obtained were equal in magnitude (30–40%) in the limbic vs. striatal brain areas; also in this respect, SCH 23390 thus differs from classical neuroleptics, which generally display more marked effects in the striatum than in limbic tissue.No major changes in the in vivo indices of NA synthesis and utilization (or in 5-HT synthesis) were found after SCH 23390 administration, by and large supporting the DA receptor specificity of the compound.In summary, the studies demonstrated that SCH 23390 can offset and accentuate, respectively, behavioural consequences of D-2 receptor stimulation and blockade. Importantly, at the same time no direct interaction at the level of D-2 DA receptor sites in the striatum was detected. Only slight, D-2 antagonist-like, changes in neurochemical indices of dopaminergic activity were observed after D-1 receptor blockade by means of SCH 23390. With regard to DA agonist hypothermia, SCH 23390 was without effect per se, but (at a high dose) attenuated the action of the D-2 antagonist haloperidol. The observations may indicate that the complex interactions between central D-1 and D-2 receptor-controlled mechanisms that influence behaviour, neurochemistry, and possibly autonomic nervous expression, are not identical.     

生物伯德图用于血压稳定性的分析和计算

本文用生物伯德图分析了血压稳定性。按照经典的控制理论,讨论了生物系统的稳定性,提出了血压控制的数学模型。根据生物特点,建立了生物伯德图的表达式。作为系统稳定性的指标,增益裕量和相位裕量可以用作图法求得,也可以用计算机求解。实验结果与理论分析能很好地符合。     

妊娠相关血浆蛋白A水平与不稳定心绞痛患者冠状动脉狭窄病变形态的关系

[目的]探讨不稳定型心绞痛患者妊娠相关血浆蛋白(PAPP-A)水平与高敏C-反应蛋白(hs-CRP)及动脉粥样硬化斑块稳定性的关系.[方法]不稳定型心绞痛组患者42例,稳定型心绞痛组38例.冠状动脉造影前检测PAPP-A和hs-CRP,根据造影结果将冠状动脉病变分为复杂狭窄和光滑狭窄.[结果]稳定型心绞痛组有28例(74%)患者至少有1支血管狭窄≥70%,多于不稳定型心绞痛组的24例(57%),P＜0.05;不稳定型心绞痛组中33例(79%)有1处以上的复杂狭窄,多于稳定型心绞痛组(22例,58%,P＜0.05);PAPP-A与hs-CRP正相关(r=0.44,P＜0.001);不稳定型心绞痛组与稳定型心绞痛组相比,hs-CRP(4.40 mg/L±0.003 mg/L vs 0.48 mg/L±0.016mg/L,P＜0.001)和PAPP-A(18.40×10-3 U/L±0.002×10-3U/Lvs 7.79×10-3 U/L±0.001×10-3 U/L,P＜0.001),差异均有统计学意义;两组中有复杂狭窄者的PAPP-A和hs-CRP水平显著高于无复杂狭窄者.[结论]PAPP-A可作为评估冠状动脉斑块稳定性的血清学指标之一.     

An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: The influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration.

There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.     

国外用体内X射线荧光技术对人体骨铅含量研究的概况

通过介绍国外人体骨铅测量的历史背景、多种器官铅含量的对比以及体内X射线荧光技术(In vivoXRF)测定骨铅研究的近期发展状况,探讨人体骨铅含量体内X射线荧光非损伤性测定的重要意义。     

接枝环氧树脂水分散液的合成、分离与表征

控制不同的反应条件,采用甲基丙烯酸、苯乙烯与环氧树脂在丙二醇丁醚/正丁醇溶剂中接枝共聚,合成了粒径在87～104nm范围的环氧树脂水分散液。通过环己烷/乙醇和丙酮两步萃取,对接枝共聚产物进行分离,用FTIR表征,并估算了接枝共聚物的组成。实验结果表明,所制备的粒径为纳米级的环氧树脂水分散液,具有良好的机械稳定性、冻融稳定性及贮存稳定性。ξ电位测定表明,产物在pH>8的条件下更为稳定。     

SCG10 mRNA localization in the hippocampus: comparison with other mRNAs encoding neuronal growth-associated proteins (nGAPs)

SCG10 is a nerve growth factor (NGF)-inducible, neuron-specific protein whose expression is tightly correlated with axonal and/or dendritic growth. We have recently shown that the mRNA encoding SCG10 is expressed at significant levels in certain subsets of neurons in the adult rat brain, while its expression is undetectable or negligible in other non-neuronal tissues. Here we show that regional SCG10 mRNA expression in the adult mouse brain is comparable to that in the rat, however, in the hippocampus its expression profile is distinct. In the mouse, SCG10 mRNA is expressed at high levels in pyramidal cells of CA3–CA4 sub-fields of Ammon's horn and at low levels in the CA1–CA2 sub-fields, while it is found rather uniformly throughout the pyramidal cell layer of the rat hippocampus. SCG10 mRNA is not detectable in the dentate gyrus of the mouse hippocampus, although it is expressed in the rat dentate gyrus. Comparison with other mRNAs encoding neuronal growth-associated proteins (nGAPs) such as GAP-43, MAP2, α1-tubulin and stathmin suggests that dentate granule cells express a different repertoire of neuronal growth-associated genes in mouse and rat.     

Granulocyte Colony-stimulating Factor Supports Liver Regeneration in a Small-for-size Liver Remnant Mouse Model

Experimental partial hepatectomy of more than 80% of the liver weight bears an increased mortality in rodents, due to impaired hepatic regeneration in small-for-size liver remnants. Granulocyte colony-stimulating factor (G-CSF) promotes progenitor cell expansion and mobilization and also has immunomodulatory properties. The aim of this study was to determine the effect of systemically administered G-CSF on liver regeneration and animal survival in a small-for-size liver remnant mouse model. Mice were preconditioned daily for 5 days with subcutaneous injections of 5 μg G-CSF or aqua ad injectabile. Subsequently, 83% partial hepatectomy was performed by resecting the median, the left, the caudate, and the right inferior hepatic lobes in all animals. Daily sham or G-CSF injection was continued. Survival was significantly better in G-CSF-treated animals (P < 0.0001). At 36 and 48 h after microsurgical hepatic resection, markers of hepatic proliferation (Ki67, BrdU) were elevated in G-CSF-treated mice compared to sham injected control animals (P < 0.0001) and dry liver weight was increased (P < 0.05). G-CSF conditioning might prove to be useful in patients with small-for-size liver remnants after extended hepatic resections due to primary or secondary liver tumors or in the setting of split liver transplantation. Presented at the Forty-seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, May 14–19, 2006 (poster presentation).     

In vivo 13C saturation transfer effect of the lactate dehydrogenase reaction.

Lactate dehydrogenase (LDH, EC 1.1.1.27) catalyzes an exchange reaction between pyruvate and lactate. It is demonstrated here that this reaction is sufficiently fast to cause a significant magnetization (saturation) transfer effect when the 13C resonance of pyruvate is saturated by a continuous-wave (CW) RF pulse. Infusion of [2-(13)C]glucose was used to allow labeling of pyruvate C2 at 207.9 ppm to determine the pseudo first-order rate constant of the unidirectional lactate-->pyruvate flux in vivo. During systemic administration of GABAA receptor antagonist bicuculline, this pseudo first-order rate constant was determined to be 0.08+/-0.01 s-1 (mean+/-SD, N=4) in halothane-anesthetized adult rat brains. In 9L and C6 rat glioma models, the 13C saturation transfer effect of the LDH reaction was also detected in vivo. Our results demonstrate that the 13C magnetization transfer effect of the LDH reaction may be useful as a novel marker for utilizing noninvasive in vivo MRS to study many physiological and pathological conditions, such as cancer.