蛇毒溶栓素对实验动物血小板功能和环腺苷酸含量的影响

本文报道蛇毒溶栓素对实验动物血小板功能和血浆环腺苷酸含量的影响.(1)对血小板数的影响:给家犬以4 u/kg量静注1小时后,循环血的血小板数由药前130.44×10~9/L±50.02×10~9/L下降至60.20×10~9/L±20.50×10~9/L(P<0.05).(2)对血小板聚集功能的影响:猕猴和家兔分别按4 u/kg、8 u/kg量静注1小时后,对ADP诱导的血小板聚集率分别山药前的62.32±22.05%和43.66±10.60%下降至1.32±0.49%和4.95±1.96%;抑制率分别为97.50±1.75%和88.34±4.31%,与药前组相比均有非常显著的差异(P<0.001).(3)对血小板cAMP含量的影响:猕猴和家兔以蛋白竞争结合法测定血小板内cAMP的含量,药后1小时的含量65.43±31.35pmole/mg,32.25±15.43pmo1e/mg蛋白质,与药前12.02±0.95pmole/mg,4.25±3.13pmole/mg蛋白质相比有明显升高(P<0.001).     

Tau immunoreactivity and SDS solubility of two populations of paired helical filaments that differ in morphology

To further understand the processes that lead to the formation of neurofibrillary tangles from paired helical filaments (PHF) in Alzheimer brains, we studied two morphologically distinct fractions of PHF separated on sucrose density gradient. In a fraction with mostly short and non-aggregated PHF, the majority of filaments could be solubilized in SDS. In a fraction containing primarily PHF aggregated into clusters or bundles, sometimes resembling neurofibrillary tangles, filaments were less soluble in SDS. Immunogold labelling with a panel of tau-immunoreactive antibodies demonstrated that N-terminal epitopes of tau were preserved in the short filaments, but were reduced or absent in aggregated filaments. In contrast, C-terminal epitopes were present in both fractions. Furthermore, the accessibility of the microtubule-binding domain to immunolabelling was markedly impaired in short and non-aggregated filaments compared to aggregated filaments. These results are consistent with proteolytic degradation of the N-terminal epitopes and preservation of the C-terminal epitopes and the microtubule-binding domain of tau in the aggregated filaments. Partial proteolysis may be involved in the generation of aggregated PHF in neurofibrillary tangles.     

钙离子跨膜转运与血小板聚集阈值

钙离子作为第二信使物质,调节着众多的生理反映。本文从钙离子的跨膜转运对血小板聚集的影响出发,提出一种数学模型方法,力图以胞浆内游离钙浓度作为指标去研究和标志血小板的聚集特性,它从一个侧面去反映血小板的老化程度或病态程度。     

Comparative studies on thein vitro andin vivo morphology of clones of experimental CNS tumours in the rat

Summary Two sarcomas, one neurosarcoma and one polymorphous tumour of uncertain classification of the central nervous system of the rat induced by N-nitrosomethylurea or ethylnitrosourea were the source of 14 clones. The cytomorphology and the aggregation pattern of the clonesin vitro are described. The malignancy and histology were checked by homologous transplantation. All the clones formed sarcoma-like structuresin vivo, but it was difficult to decide whether these neoplasias were real sarcomas or very dedifferentiated glial tumours. The differences in cytology observedin vitro were greater than the histological differencesin vivo.     

Effect of ethanol on thrombin-induced platelet phospholipid breakdown and release of [3H]-5-hydroxytryptamine

Ethanol has been reported previously to inhibit chemically-induced platelet aggregation and the release of platelet contents. In platelet suspensions the mechanical stimulus of stirring can induce slow aggregation and the loss of endogenous arachidonic acid from phospholipids by activation of platelet phospholipases. These changes are prevented by the presence of ethanol 20-100 mM, whereas, in unstirred suspensions, ethanol alone has no effect on platelet phospholipids. Under similar conditions of reduced platelet: platelet contact, chemical stimuli, such as thrombi, although unable to produce visible aggregation, still cause the release of [3H]-5-hydroxytryptamine from platelets and also initiate the breakdown of platelet phospholipids. Ethanol does not now inhibit the thrombin-induced release of platelet contents and has little effect on phosphatidylinositol breakdown, though it inhibits phosphatidylcholine breakdown. Ethanol may therefore inhibit platelet aggregation by reducing the effect of mechanical and chemical stimuli on the activation of phospholipase A2. In contrast ethanol has rather little effect on the receptor-mediated breakdown of phosphatidylinositol which is apparently sufficient to trigger the release of platelet contents.     

Comparison between induced platelet aggregation and circulating platelet aggregates as platelet function tests in patients with transient ischemic attacks

Routine blood analysis, platelet counts, number of circulating platelet aggregates (CPA) and platelet aggregation in vitro against adenosine-diphosphate (ADP), epinephrine and collagene were studied in 45 healthy controls, in 10 hospitalized patients with other neurological diseases than stroke and in 12 patients with transient ischemic attacks (TIA) before and after prophylactive treatment with anticoagulants (AC) or anti-platelet drugs (APD).
Except for lower hemoglobin and hematocrit levels in women, sex, smoking, oral contraceptives or pregnancy did not significantly influence the routine blood parameter. Smoking females taking oral contraceptives had an increased number of CPA and the most easily induced aggregation in vitro .
Patients with TIA had no significant differences in blood or platelet findings versus the healthy controls (except smoking females on oral contraceptives) or the non-stroke patients, even though individual patients could have high numbers of CPA and an easily induced platelet aggregation in vitro . Treatment with AC did not influence platelet function, whereas APD therapy decreased the number of CPA and inhibited the secondary platelet aggregation in vitro .     

The ontogeny of aggregation-enhanced toxicity

Sensitivity to the lethal effects of methamphetamine was observed under grouped conditions relative to isolated conditions in rats 25 and 30 days old but not in rats 7, 10, 15, or 20 days of age. Results are interpreted in terms of the development of the central catecholaminergic systems through which methamphetamine is thought to induce toxicity.Supported by Searle Fellowship     

Mutual Stimulation of Beta-Amyloid Fibrillogenesis by Clioquinol and Divalent Metals

As reported by some authors, clioquinol (CQ), a 8-hydroxyquinoline derivative, has produced very encouraging results in the treatment of Alzheimer’s disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper (II) and zinc (II), critically associated with β-amyloid (Aβ) aggregation/fibrillogenesis and degeneration processes in the brain. The present study was aimed at assessing the in vitro effects of CQ on the aggregation/fibrillogenesis properties of human Aβ either alone or complexed with Cu²⁺ and Zn²⁺. Surprisingly, our data indicated that CQ promoted rather than inhibited the formation of Aβ fibrillar aggregates when added metal ions were present. To understand whether the latter effects were related to the peptide amino acid sequence, we also investigated the aggregational profile of rat Aβ, which differs from the human homologous for three amino acidic substitutions. Such a sequence alteration drastically reduced the tendency of the peptide to undergo spontaneous aggregation/fibrillization. In the presence of CQ and metals, however, also rat Aβ showed a strong propensity to generate fibrillar aggregates. In agreement with the pro-aggregation effects observed in solution, studies with neuroblastoma cells demonstrated an impairment of cell functioning only in the presence of CQ + Aβ–metals. Based on the present findings, the literature data on the potential effectiveness of CQ-based chelation therapy in AD should be re-interpreted. An erratum to this article can be found at     

Effects of thromboxane synthetase inhibitors on aggregation of rabbit platelets

Thromboxane (TX) synthetase activity was selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) and sodium (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methyl-propenoate (OKY-1581) (OKYs). Their IC₅₀ for the rabbit platelet enzyme were found to be 11nM and 3nM respectively. Arachidonic acid (AA) or collagen induced platelet aggregation, and generated TXA₂ and prostaglandins (PGs) in rabbit platelets. OKYs inhibited platelet aggregation and TXA₂ generation without affecting PGs generation, while aspirin inhibited platelet aggregation, and TXA₂ and PGs generation. There was a parallel relation between the degree of inhibition of platelet aggregation and TXA₂ generation by OKYs, but the inhibitory effects of aspirin on platelet aggregation was related to that on both TXA₂ and PGs generation. However, OKYs and aspirin did not inhibit ADP-induced platelet aggregation which did not involve the generation of TXA₂ and PGs. These results suggested that TXA₂ generation is related to platelet aggregation induced by AA or collagen, and that the inhibitory effect of OKYs on platelet aggregation is due to the inhibition of TX synthetase.