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101.
明胶-聚乳酸载药纳米微球的制备及其体外释药研究 总被引:21,自引:0,他引:21
采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球,以混合型乳化剂Tween—80:Span—80=5:1—作为初乳乳化剂,O—羧甲基壳聚糖作为复乳乳化剂,考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响,经优化条件得到了成球性和体外释放都比较好的载药微球。 相似文献
102.
The inhibitory effect of a high external Ca2+ ([Ca2+]o) on spontaneous transmitter release in a high K+ solution (Gage and Quastel 1966; Birks et al. 1968) was studied at the frog neuromuscular junction, based on the hypothesis that an increased intracellular free Ca2+ ([Ca2+]i) in the nerve terminal plays a key role in the depression. Three procedures were employed to increase [Ca2+]i; increasing [Ca2+]o, application of caffeine and tetanic nerve stimulation. All of these procedures increased m.e.p.p. frequency in normal Ringer. However, as the basic m.e.p.p. frequency was increased by raising the external K+ concentration (7–15 mM), their facilitatory effects on m.e.p.p. frequency decreased, disappeared and eventually reversed to depressant actions. Since a rise in the external K+ concentration would increase the steady state level of [Ca2+]i, it is suggested that when the [Ca2+]i is preset at a high level, manipulations so as to further increase [Ca2+]i depress spontaneous release of transmitter. Possible mechanisms for this inhibition was discussed in relation to a question whether or not the rate of spontaneous transmitter release is a monotonic function of [Ca2+]i. 相似文献
103.
104.
Rodrigo A. Cunha A. M. Sebastião 《Pflügers Archiv : European journal of physiology》1993,424(5-6):503-510
The independent release of adenosine and adenine nucleotides upon electrical stimulation was studied in the innervated sartorius muscle of the frog after blockade of the extracellular catabolism of adenosine monophosphate (AMP) through exo-AMP deaminase and ecto-5-nucleotidase. Nerve stimulation (30 min, 0.2Hz) induced the release of both adenosine (19±3 pmol) and adenine nucleotides (101±7 pmol). Experiments performed in the presence of tubocurarine (5 M) to prevent purine release due to nerve-evoked muscle twitching, or under direct stimulation of the muscle in low calcium solutions to prevent pre-synaptic release of purines, showed that there was an evoked release of adenosine and adenine nucleotides both from the nerve endings and from the twitching muscle fibres. Removal of ecto-5-nucleotidase inhibition shows that the catabolism of adenine nucleotides released during stimulation contributes in about 50% to the amount of endogenous extracellular adenosine. When only one of the enzymes catabolizing AMP (ecto-5-nucleotidase or exo-AMP deaminase) was inhibited, the evoked release of adenine nucleotides was undetectable, suggesting that each enzyme is able to catabolize all the AMP formed from adenine nucleotides released upon stimulation. It is concluded that the concentration of endogenous extracellular adenosine is under the control of the relative activities of exo-AMP deaminase and ecto-5-nucleotidase.Brief accounts of some of the results in this study have been published previously (refs. [6, 7]). 相似文献
105.
目的 将氢化可的松与壳聚糖进行偶连,以改善其溶解性,延缓其释放。方法以琥珀酰基为连接臂将氢化可的松与壳聚糖进行偶连(N-氢化可的松琥珀酰基壳聚糖),并通过红外及紫外光谱对偶连物的化学结构进行确证,分别采用溶解实验的方法及动态透析法考察偶连物的溶解性及体外释放特征。结果当氢化可的松琥珀酰基的取代度为15.5%时,N-氢化可的松琥珀酰基壳聚糖易溶于酸性水溶液,而在中性及弱碱性水溶液中形成凝胶;其体外释放速度缓慢,36h内的总释放量为5.8%。结论 壳聚糖作为氢化可的松的高分子载体,能明显改善其溶解性,延缓其释放。 相似文献
106.
Matthias Gansel Reinhold Penner Florian Dreyer 《Pflügers Archiv : European journal of physiology》1987,409(4-5):533-539
(1) We investigated the effects of single- and double-poisoning with tetanus toxin (TeTx), botulinum neurotoxin type A (BoTx A) and botulinum neurotoxin type B (BoTx B) on spontaneous and nerve-evoked quantal transmitter release at motor endplates of the triangularis sterni preparation of the mouse. (2) Inhibitory effects of TeTx and BoTx B on spontaneous and nerve-evoked transmitter release were very similar, except that the action of BoTx B required 500-fold lower concentrations and was less dependent on temperature. BoTx A caused stronger inhibition of quantal release than TeTx or BoTx B, but was comparatively much easier counteracted by 4-aminopyridine (4-AP). (3) In contrast to BoTx A, with TeTx or BoTx B the increase of transmitter release following onset of 50 Hz nerve stimulation was delayed for a few seconds and synaptic latencies of quanta showed large variations. This release pattern was also evident in all double-poisoning experiments, regardless of intoxication sequence. (4) Inhibition of evoked release was found to be slightly stronger with TeTx than with BoTx B, so the amount of nerve-evoked quanta released after double-poisoning with any sequence of these toxins always approached that of TeTx. In no case supraadditive actions were observed. (5) A strong reduction of evoked quanta was observed when BoTx A was applied in addition to either of the two other toxins. With reversed poisoning sequences (BoTx A-TeTx or BoTx A-BoTx B) the resulting values remained at the extremely low level of BoTx A. (6) In the presence of 4-AP double-poisoning with any combination between BoTx A and TeTx or BoTx B (regardless of intoxication sequence) revealed supra-additive effects, since the number of quanta released was considerably lower than that obtained with any of the toxins alone (in the presence of 4-AP). (7) Our results indicate that tetanus toxin and botulinum toxin type B have a common site of action which is different and independent from that of botulinum toxin type A.This is part of the thesis of M. G. to be presented to the Fachbereich Humanmedizin, Justus-Liebig-Universität Gießen 相似文献
107.
Kyoko Hayashi 《Journal of medical virology》1995,47(4):323-329
Before completion of polarization, Madin-Darby canine kidney (MDCK) cells showed high infectivity and progeny production of herpes simplex virus type 1 infection. After polarization or formation of tight junctions, the infectivity and virus replication in MDCK cells was restricted significantly. The disruption of tight junctions by depletion of Ca2+ resulted in increasing virus infectivity and productivity. Mechanical disruption of tight junctions by scratching the cell monolayers with injection needle allowed markedly the replication of HSV-I in the cells aligned along the injured area. In polarized MDCK cells the progeny were released preferentially from the apical surface of the cells. These data suggest that because polarized MDCK cells mimic the epithelial cell layers, this cell line is helpful for determining the factors which regulate viral transmission in the human body. © Wiley-Liss, Inc. 相似文献
108.
Elisabeth Arnauld John du Pont 《Pflügers Archiv : European journal of physiology》1982,394(3):195-201
A close relationship exists between drinking and the release of vasopressin, the two main factors responsible for the maintenance of body water content. Whereas the participation of peripheral factors, such as oropharyngeal stimulation, seems obvious in the metering of fluid intake and in thirst satiation, very little is known about their influence on vasopressin release. In the present experiments, the influence of drinking on vasopressin release was studied using both biochemical and electrophysiological approaches.In one group of monkeys made thirsty by water deprivation, the subsequent drinking of water during a 5–8 min induced: i) a short-term response, consisting of an abrupt fall in plasma vasopressin concentration which was independent of osmolality, occurred at the time of drinking and was partly reversed after the cessation of drinking, and ii) a longer lasting response, consisting of a slow diminution of plasma vasopressin concentration as the intestinal absorption of water progressed. In another group of thirsty monkeys, extracellular recordings were made during drinking from cells which were identified as neurosecretory neurones of the supraoptic nucleus, a number of them being considered vasopressin secreting on the basis of their phasic pattern of firing. Their firing decreased considerably during the periods of water intake and recovered to control levels immediately after-wards.The decrease in vasopressin release at the onset of water intake, the diminution in the firing rate of the neurones, the short latency and the reversibility of these events after cessation of drinking, suggest that a reflex inhibition of vasopressin-secreting neurones occurs which is probably induced by peripheral stimuli and most likely via oropharyngeal or other visceral receptors. It is postulated that this reflex inhibition of vasopressin release may participate in some active manner in the anticipatory mechanisms of thirst satiation. 相似文献
109.
Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child 总被引:2,自引:0,他引:2
Paananen A Ylipaasto P Rieder E Hovi T Galama J Roivainen M 《Journal of medical virology》2003,69(4):529-537
The full-length infectious cDNA clone was constructed and sequenced from the strain DM of echovirus 9, which was recently isolated from a 6-week-old child at the clinical onset of type 1 diabetes. Parallel with the isolate DM, the full-length infectious cDNA clone of the prototype strain echovirus 9 Barty (Barty-INF), was constructed and sequenced. Genetic relationships of the sequenced echo 9 viruses to the other members of the human enterovirus type B species were studied by phylogenetic analyses. Comparison of capsid protein sequences showed that the isolate DM was closely related to both prototype strains: Hill and Barty-INF. The only exception was the inner capsid protein VP4 where serotype specificity was not evident and the isolate DM clustered with the strain Hill and the strain Barty-INF with echovirus 30 Bastianni. Likewise, the nonstructural protein coding region, P2P3, of isolate DM was more similar to strain Hill than to strain Barty-INF. However, like echovirus 9 Barty, the isolate DM contained the RGD-motif in the carboxy terminus of capsid protein VP1. By blocking experiments using an RGD-containing peptide and a polyclonal rabbit antiserum to the alpha(v)beta(3)-integrin, it was shown that this molecule works as a cellular receptor for isolate DM. By using primary human islets, it was shown that the isolate DM is capable of infecting insulin-producing beta-cells like the corresponding prototype strains did. However, only isolate DM was clearly cytolytic for beta-cells. The infectious clones that were made allow further investigations of the molecular features responsible for the diabetogenicity of the isolate DM. 相似文献
110.
Sue Piper Duckles 《Neurobiology of aging》1983,4(2):151-156
The adrenergic control of vascular smooth muscle was compared in young and adult rabbits using a variety of in vitro techniques. Norepinephrine (NE) content and accumulation of 3H-NE were not different in blood vessels from the two age groups. In contrast, stimulation-evoked release of endogenous NE was reduced by 40–60% in vessels from the aged animals. Functional studies of smooth muscle contractions were carried out using isolated ring segments of the ear artery. There were no differences in the resting force-response relationship between vessels from young and adult rabbits. Maximum contractile responses to nerve stimulation, NE or KCl were not different in vessels from the two age groups, nor was the NE ED50. However, blockade of the neuronal uptake system with desmethylimipramine produced a greater shift in the NE concentration-response curve in vessels from the young animals compared to the shift in vessels from adult animals. This observation reflects a decline in neuronal NE uptake with age. Although maximal contractile responses to transmural nerve stimulation at 16 Hz were unchanged, responses to stimulation at lower frequencies were reduced in vessels from adult rabbits, an effect which was also enhanced when an antagonist of neuronal uptake was present. Thus, there is a decline in function of adrenergic nerves in adult animals, reflected in a decrease in stimulation-evoked NE release and a decrease in norepinephrine uptake revealed by functional studies. These two effects tend to balance each other, so that there is a small decrease in contractile response to adrenergic nerve stimulation which is exacerbated when neuronal uptake mechanisms are blocked. 相似文献