Influence of liposome charge and composition on their interaction with human blood serum proteins

The roles of sulfhydryl and disulfide groups in the specific binding of synthetic cannabinoid CP-55,940 to the cannabinoid receptor in membrane preparations from the rat cerebral cortex have been examined. Various sulfhydryl blocking reagents including p-chloromercuribenzoic acid (p-CMB), N-ethylmaleimide (NEM), o-iodosobenzoic acid (o-ISB), and methyl methanethiosulfonate (MMTS) inhibited the specific binding of [³H]CP-55,940 to the cannabinoid receptor in a dose-dependent manner. About 80–95% inhibition was obtained at a 0.1 mM concentration of these reagents. Scatchard analysis of saturation experiments indicates that most of these sulfhydryl modifying reagents reduce both the binding affinity (K_d) and capacity (B_max). On the other hand, DL-dithiothreitol (DTT), a disulfide reducing agent, also irreversibly inhibited the specific binding of [³H]CP-55,940 to the receptor and about 50% inhibition was obtained at a 5 mM concentration. Furthermore, 5mM DTT was abelt to dissociate 50% of the bound ligand from the ligand-receptor complex. The marked inhibition of [³H]CP-55,940 binding by sulfhydryl reagents suggests that at least one free sulfhydryl group is essential to the binding of the ligand to the receptor. In addition, the inhibition of the binding by DTT implies that besides free sulfhydryl group(s), the integrity of a disulfide bridge is also important for [³H]CP-55,940 binding to the cannabinoid receptor.     

腺苷在低氧适应家兔脑血流调节中的作用

本研究观察了腺苷在低氧适应家兔脑血流(CBF)调节中的作用。结果表明:缺氧时适应组CBF改变不明显,对照组CBF明显增加;缺氧时适应组脑腺苷的含量明显低于对照组,而脑腺苷酸的含量明显高于对照组;适应组脑微血管对腺苷的反应与对照组相近。提示缺氧时低氧适应家兔CBF改变不明显,同低氧适应后脑腺苷含量较低、腺苷酸含量较高有关。     

丹参素注射液对急性心肌梗死大鼠的心室重构、心室功能及肢体导联与胸导联心电图参数的影响

摘要 目的：探讨丹参素注射液对急性心肌梗死大鼠的心室重构、心室功能及肢体导联与胸导联心电图参数的影响。方法：选择SD大鼠40只,将其鼠随机模型组、假手术组、硝酸甘油组、丹参注射液组。假手术组大鼠给予只在冠状动脉处穿针,不进行结扎,其余步骤同其余3组,其余3组均进行动物模型构建。假手术组、模型组大鼠均腹腔注射氯化钠注射液,硝酸甘油组腹腔注射硝酸甘油,丹参注射液组腹腔注射丹参注射液。对比4组大鼠的肢体导联与胸导联心电图参数,对比4组大鼠的血液流变学指标、左心室功能及左心室重构。结果：模型组的Ⅰ、Ⅱ、Ⅲ、aVL、aVF、V1、V2、V5、血浆粘度、纤维蛋白原、红细胞聚集指数、舒张末期室间隔厚度、左室舒张末期内径、左室收缩末期内径、左室舒张末期容积、左室收缩末期容积明显较假手术组、硝酸甘油组、丹参注射液组高,硝酸甘油、丹参注射液组以上指标明显较假手术组高,模型组的的左室舒张末期厚度、左室射血分数、左室短轴缩短率明显较假手术组、硝酸甘油组、丹参注射液组低,硝酸甘油、丹参注射液组的左室舒张末期厚度、左室射血分数、左室短轴缩短率明显较假手术组低。模型组的左心室重量指数、左心室截面直径明显较假手术组、硝酸甘油组、丹参注射液组高,硝酸甘油、丹参注射液组的左心室重量指数、左心室截面直径、梗死面积明显较假手术组高（P<0.05）,硝酸甘油组与丹参注射液组以上指标对比无差异（P>0.05）。结论：丹参素注射液可改善急性心肌梗死大鼠的心室重构、左心室功能及肢体导联与胸导联心电图参数,可能与其可降低大鼠的血液流变学指标水平有关。     

Incomplete cerebral ischemia in the rat provokes increase of tissue and plasma malondialdehyde

Short-term incomplete cerebral ischemia was induced in the rat by bilaterally clamping for 5 min the common carotid arteries; subsequent reperfusion of 10 min was obtained by removing carotid occlusion. At the end of ischemia or reperfusion, animals were sacrificed by decapitation. A control group was represented by sham-operated rats. Peripheral venous blood samples were withdrawn from the femoral vein from rats subjected to cerebral reperfusion 5 min before ischemia, at the end of ischemia, and 10 min after reperfusion. A highly sensitive HPLC method for the direct determination of malondialdehyde, oxypurines, and nucleosides was used on 200 μL of brain tissue and plasma extracts. Incomplete cerebral ischemia induced the, appearance of a significant amout of tissue malondialdehyde (undetectable in control animals) and a decrease of ascorbic acid. A further 6.6-fold increase of malondialdehyde and a 18.5% decrease of ascorbic acid occurred after 10 min of reperfusion. Plasma malondialdehyde, which was present in minimal amount before ischemia, significantly increased after 5 min of ischemia, being strikingly augmented after 10 min of reperfusion. A similar trend was observed for oxypurines and nucleosides. From these data, it can be affirmed that tissue concentrations of malondialdehyde and ascorbic acid, and plasma levels of malondialdehyde, oxypurines, and nucleosides, reflect both the oxygen radical-mediated tissue injury and the depression of energy metabolism thus representing early biochemical markers of short-term incomplete brain ischemia, and reperfusion in the rat.     

Space proton flux and the temporal distribution of cardiovascular deaths

 The influence of solar activity (SA) and geomagnetic activity (GMA) on human homeostasis has long been investigated. The aim of the present study was to analyse the relationship between monthly proton flux (>90 MeV) and other SA and GMA parameters and between proton flux and temporal (monthly) distribution of total and cardiovascular-related deaths. The data from 180 months (1974–1989) of distribution in the Beilinson Campus of the Rabin Medical Centre, Israel, and of 108 months (1983–1991) from the Kaunas Medical Academy, were analysed and compared with SA, GMA and space proton flux (>90 MeV). It was concluded: (1) monthly levels of SA, GMA and radiowave propagation (Fof2) are significantly and adversely correlated with monthly space proton flux (>90 MeV); (2) medical-biological phenomena that increase during periods of low solar and/or geomagnetic activity may be stimulated by physical processes provoked by the concomitant increase in proton flux; (3) the monthly number of deaths related (positively or negatively) to SA are significantly and adversely related to the space proton flux (>90 MeV). Received: 14 January 1996 / Accepted: 14 October 1996     

Baclofen is cytoprotective to cerebral ischemia in gerbils

The release of the neurotransmitter, glutamate, and the activation of receptor operated calcium channels, may increase the degree of damage in ischemic brain tissue. Inhibition of excitatory neurotransmitters should therefore result in cytoprotection of ischemic brain tissue. In this study we evaluated the effect of baclofen, an inhibitor of presynaptic glutamate release, on ischemic gerbil cortex, hippocampus (CA 1 and CA4), striatum and thalamus. Histological evaluation was done in a blind manner in 4 groups (total 36 animals): a control group (9 animals) and three groups (27 animals) with varying doses of baclofen. For cerebral ischemia, we used single episode of five minutes of arterial occlusion of the carotid arteries. Baclofen in doses of 0, 25, 50, and 100 mg/kg were given to different groups five minutes prior to ischemic insult. This was followed by intraperitoneal injections given 24 and 48 hours after the initial insult. Statistically significant histological cytoprotection was demonstrated. Doses of 25 mg/kg appeared to demonstrate significant protection of the cortex (p=0.0002), the CA1 and CA4 regions of the hippocampus (p=0.0004 and 0.0001) respectively. At a dose of 50 mg/kg, significant cytoprotection was demonstrated at the hippocampus (CA1 and CA4 regions), in particular at the CA4 region (p=0.0029). The 100 mg/kg dose appeared to have most significant protection at the CA1 and CA4 regions of the hippocampus (both p=0.0001), striatum (p=0.0011), and the thalamus (p=0.0008). All statistical comparisons were done using non-parametric tests (Mann-Whitney U test). Our study demonstrates that baclofen is cytoprotective to ischemic neuronal cells, especially in the hippocampus. Clinically this may be beneficial to those patients with strokes or head injuries.     

Structural alterations in synaptosomal membrane-associated proteins and lipids by transient middle cerebral artery occlusion in the cat

We have previously reported that ischemia reperfusion injury results from free radical generation following transient global ischemia, and that this radical induced damage is evident in the synaptosomal membrane of the gerbil. [Hall et al, (1995) Neuroscience 64: 81–89] In the present study we have extended these observations to transient focal ischemia in the cat. We prepared synaptosomal membranes from frontal, parietal-temporal, and occipital regions of the cat cerebral cortex with reperfusion times of 1 and 3 hours following 1 hour right middle cerebral artery occlusion. The membranes were selectively labeled with protein and lipid specific paramagnetic spin labels and analyzed using electron paramagnetic resonance spectrometry. There were significant motional changes of both the protein and lipid specific spin labels in the parietal-temporal and occipital regions with 1 hour reperfusion; but, both parameters returned to control values by 3 hours reperfusion. No significant changes were observed in the normally perfused frontal pole at either reperfusion time. These results support the argument that free radicals play a critical role in cell damage at early reperfusion times following ischemia.     

大脑皮层神经元膜蛋白构象改变的ESR研究

采用马来酰亚胺标记完整的大脑皮层细胞,观察由低氧引起的ESR谱线的变化及脑细胞脂质过氧化程度,低氧引起细胞过氧化物生成增加,膜蛋白构象改变．金属硫蛋白(10^-5mol/L)能明显抑制过氧化反应,具有一定的抗氧化作用．并对实验的分子机理进行了简要的讨论．     

The Effect of Cyclohexyladenosine on the Penischemic Increases of Hippocampal Glutamate and Glycine in the Rabbit

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)