SiO2对肺泡巨噬细胞活性氧释放和脂质过氧化的影响

利用体外实验系统初步研究了SiO_2对肺泡巨噬细胞活性氧释放与诱发脂质过氧化的影响。结果表明,SiO_2对肺泡巨噬细胞活性氧的释放主要呈剂量与时间依赖性的抑制效应,这一抑制效应与SiO_2对细胞质膜的损伤作用密切相关。在SiO_2作用早期刺激巨噬细胞活化的程度与时程,可能主要取决于SiO_2对膜损伤的程度。而SiO_2引起的巨噬细胞脂质过氧化,似乎并非是由于SiO_2诱发巨噬细胞产生过多的活性氧自由基的结果。     

Prediction of the stability of polymeric matrix tablets containing famotidine from the positron annihilation lifetime distributions of their physical mixtures

The aim of the present work was to elucidate the impact of the structural changes of polymeric excipients during the course of storage on the drug release stability of tablets containing different polymers. Matrix tablets were formulated with famotidine as a model drug, using polyvinylpyrrolidone and carbopol matrix. Dissolution tests were carried out before and after storing the tablets under stress conditions for different time intervals. Parameters characterizing the release kinetics of matrix tablets, just as difference and similarity factors, were calculated to compare the release profiles as a function of storage time. Positron annihilation lifetime measurements were carried out to track the structural changes of the physical mixtures containing polymers during the course of storage. The changes in the positron lifetime distribution curves of the famotidine-polymer mixtures were in good correlation with the significant changes of release parameters of tablets. Thus the method would be a valuable tool for the screening of possible destabilizing interactions in the preformulation phase.     

Levetiracetam extended release and levetiracetam immediate release as adjunctive treatment for partial-onset seizures: An indirect comparison of treatment-emergent adverse events using meta-analytic techniques

The safety profiles of once-daily adjunctive levetiracetam (LEV) extended release (XR) (1000 mg/day) and adjunctive LEV immediate release (IR) (500 mg twice daily) were compared using data from three randomized, placebo (PBO)-controlled phase III clinical trials in patients with partial-onset seizures. MedDRA 9.0 treatment-emergent adverse events (TEAEs) were indirectly compared using meta-analytic techniques, including calculation of risk difference (RD) and mixed-effects analysis. Statistical significance was set at 10% alpha risk, the normative value for these analyses. Data from 555 patients older than 16 (204 LEV IR, 70 LEV XR, 281 PBO) were analyzed. Following adjustment for incidence of placebo TEAEs, LEV XR showed statistically significantly lower rates of TEAEs than LEV IR across nervous system disorders (RD = −18%, P = 0.03), psychiatric disorders (RD = −11%, P = 0.08), and metabolism and nutrition disorders (RD = −3%, P = 0.08). Among nervous system disorders, the RD for headache favored LEV XR (RD = −11%, P = 0.08). These results suggest that adjunctive LEV XR may be associated with a lower incidence of nervous system, psychiatric, and nutritional and metabolic TEAEs as compared with LEV IR. However, this difference was observed at a broad scale and not at a specific TEAE level except for headache.     

Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro

The effects of glucose deficiency on (1) the K⁺-evoked release of glutamate and aspartate and (2) excitatory synaptic transmission were studied in the Schaffer collateral-commissural-ipsilateral associational (SCCIA) projection to area CA1 of the rat hippocampal formation in vitro. Compared with 1 or 10 mM glucose, superfusion of CA1 slices with 0.1 mM glucose enhanced the K⁺-evoked release of both glutamate and aspartate, increased the ratio of aspartate release to glutamate release and did not affect the release of GABA. With both high and low glucose concentrations, the K⁺-evoked release of glutamate and aspartate originated predominantly from a Ca²⁺-sensitive store associated with the SCCIA projection. Superfusion with glucose-deficient medium abolished the inhibitory effect of adenosine on glutamate and aspartate release, but augmented the enhancing effect of the adenosine antagonist 8-phenyltheophylline. These results suggest that enough endogenous adenosine was released from the slices under these conditions to saturate the presynaptic A1 receptors. Despite its facilitatory effect on excitatory transmitter release, glucose-deficient medium inhibited transmission at Schaffer collateral-commissural synapses. Even when the postsynaptic response to a single electrical pulse was abolished, however, a substantial response could still be evoked through paired-pulse or frequency potentiation and the inhibition promptly reversed upon superfusion with 10 mM glucose. The increased ratio of aspartate release to glutamate release appears to reflect changes in the tissue content of these amino acids. The enhanced release of both excitants is suggested to result partly from a rise in intraterminal Ca²⁺ concentration and partly from inhibition of glutamate/aspartate uptake. Enhanced aspartate release may be particularly relevant to hypoglycemic damage in the CA1 area, because aspartate is a more potent hippocampal excitotoxin than glutamate.     

A Study on Hypotensive Action of Total Saponin of Ziziphus Jujuba Mill and Its Mechanism

Total saponin of Ziziphus Jujuba Mill seeds(ZS) produced amarked hvpotensive effect in anesthetized Sprague-Dawley rats(I. V. or I. P. )and cats (I. V. ). ZS showed no effect on the pressor effect of nor-adrenalinein rats. the depressor effect of ZS was not influenced by atropine nor bydiphenhydramine. ZS markedly inhibited the pressor reflex in catsinduced by ocelusion of the common carotid artery. In rats, ZS inhibitedthe spontaneous discharges of the preganglionic fibers of the greatersplanchnic nerve and decreased the plasma renin activity. These resultsshowed that the hypotensive action of ZS was probably central in origin.     

Is elevated noradrenaline an aetiological factor in a number of diseases?

1 Here I put forth the hypothesis that noradrenaline (NA), which is a signalling molecule in the brain and sympathetic nervous system (SNS), is an aetiological factor in a number of diseases. 2 In a previous paper ( Fitzgerald, Int. J. Cancer, 124 , 2009 , 257), I examined evidence that elevated NA is a factor in various types of cancer. Here I extend the argument to several other diseases, including diabetes mellitus, open‐angle glaucoma, osteoarthritis and rheumatoid arthritis and asthma. 3 The principal hypothesis is that, largely as a result of genetics, elevated noradrenergic tone in the SNS predisposes a large number of individuals to a broad range of diseases. 4 For each of the above five diseases, I briefly examine the following four lines of evidence to assess the hypothesis: i) whether pharmacological studies in rodents that manipulate NA levels or receptors affect these diseases; ii) whether pharmacological manipulation of NA in humans affects these diseases; iii) whether bipolar disorder, excessive body weight, and hypertension, which may all three involve elevated NA, tend to be comorbid with these diseases and iv) whether psychological stressors tend to cause or exacerbate these conditions, since psychological stress is associated with increased release of NA. 5 The four lines of evidence tend to support the hypothesis.     

Carotid occlusion increases the release of endogenous GABA in the nucleus of the solitary tract

Summary In anaesthetized cats, the nucleus of the solitary tract was bilaterally superfused through push-pull cannulae with artificial cerebrospinal fluid (CSF) and the effect of carotid occlusion on the release of endogenous GABA was investigated.Bilateral carotid occlusion led to a rise in blood pressure which was associated with a very pronounced increase in the release rate of GABA in the nucleus of the solitary tract. The results demonstrate the hypertensive function of GABA in the nucleus of the solitary tract and the importance of GABAergic neurons of this nucleus for the central cardiovascular control.This work was supported by the Fonds zur Fbrderung der wissenschaftlichen Forschung Send offprint requests to A. Philippu at the above address     

Cell cycle synchronization

The yeast Saccharomyces cerevisiae has been an excellent model system for cell cycle studies. Many such studies require cells synchronized in some particular portion of the cell cycle. Here, methods are described for obtaining and examining synchronized cells as they pass through one or more rounds of the cell cycle. The methods are of two types. First, block-and-release methods, where cells are initially synchronized by blocking them at some particular cell cycle stage, then releasing them from the block under conditions suitable for growth, and taking samples at different times after the release, thereby obtaining samples representing different cell cycle stages. The second type of method is elutriation. Centrifugal elutriation can be used to obtain samples of uniformly sized cells, and because cell size is correlated with cell cycle stage, these cells are synchronized with respect to their position in the cycle. Because elutriation is a very different method from block- and-release, it is ideal as a second method of synchronization to ensure that results achieved by block-and-release are not artefactual. Here, block-and-release experiments with the mating pheromone alpha factor, and with the cdc15-2 mutation, are described in detail, as are some elutriation methods.     

Central effects of tetanus and botulinum neurotoxins

Tetanus neurotoxin (TeNT) and botulinum neurotoxins (BoNTs; from A to G) are metalloproteases that act on nerve terminals to prevent exocytosis. They are extensively exploited for the study of cellular physiology. Moreover, BoNTs are also employed in clinical neurology for the treatment of several disorders characterized by hyperexcitability of peripheral nerve terminals. This review summarizes recent studies that have provided a deeper understanding of the mode of action of TeNT and BoNTs. TeNT and BoNTs bind with extreme specificity and are internalized at the neuromuscular junction. We first examine the retrograde transport mechanisms by which TeNT gains access to the central nervous system. We also discuss recent findings indicating that, besides their well known local actions at the neuromuscular junction, BoNTs can also affect central circuits.     

咪唑斯汀治疗慢性荨麻疹30例临床疗效观察

目的：观察咪唑斯汀治疗慢性荨麻疹的疗效观察。方法：慢性荨麻疹患者30例口服咪唑斯汀10mg 1次/d,共两周进行临床观察。结果：治疗30例慢性荨麻疹有效率在第7天和第14天后分别为66.7%和93.3%。治疗过程中不良反应仅为6.7%,且症状轻。结论：咪唑斯汀治疗慢性荨麻疹简便、安全、有效。