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1.
目的观察急性缺血性脑卒中大鼠脑内髓鞘碱性蛋白(MBP)基因的表达情况,探讨针刺疗法干预急性缺血性脑卒中病理过程的机制。方法采用缺血性脑卒中大鼠模型,应用反转录-聚合酶链反应半定量法,观察比较正常组与缺血性脑卒中对照组、早期针刺组、晚期针刺组缺血后1、3、5、7d的MBP基因表达的变化。结果对照组MBP基因的表达随时间先减少后增多,早、晚期针刺组MBP基因的表达不断增强,但早期针刺组增强效果更明显。结论针刺对缺血性脑损伤的保护效应可能与促进脑内MBP基因的表达进而促进髓鞘的再生有关。 相似文献
2.
The subcellular distribution of basic substances such as mepacrine, chloroquine, chlorpromazine and imipramine was studied in rabbit blood platelets exposed to these compounds in vitro and to some in vivo. All the drugs showed a preferential concentration in the 5-hydroxytryptamine (5HT) storage organelles (5HT vesicles). Chloroquine and mepacrine accumulated more specifically in the organelles than did chlorpromazine and imipramine. After osmotic shock of the 5HT vesicles chlorpromazine sedimented mostly with the vesicular membranes, whereas the other compounds preferentially went into the supernatant. It is concluded that (a) fluorescent basic compounds such as mepacrine are rather specific markers for the 5HT storage organelles in live platelets and (b) drugs such as chlorpromazine and imipramine also have a considerable affinity for these organelles. 相似文献
3.
Hubert Affolter Paul Erne Ernst Bürgisser Alfred Pletscher 《Naunyn-Schmiedeberg's archives of pharmacology》1984,325(4):337-342
Summary In blood platelets of man, both 5-hydroxytryptamine (5HT) and 80 nM of the Ca2+-ionophore A23187 led to rapid shape change reactions which were inhibited by prostaglandin E1 (PGE1), forskolin, 2-methyl-6-methoxy-8-nitroquinoline (quin2) and chlortetracycline. The IC50-values of the inhibitors were similar in the 5HT- and the A23187-experiments. Higher amounts of A23187 abolished the inhibitory actions of PGE1 and forskolin. Furthermore, 5HT and A23187 enhanced adrenaline-induced platelet aggregation their effects showing similar time dependence. Ketanserin, an antagonist of 5HT2-receptors, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular Ca2+-antagonist, counteracted the effects of 5HT much more than those of A23187, whereas acetylsalicylate and indomethacin did not influence the actions of either 5HT or A23187. In addition, 5HT caused a concentration-dependent rise of intracellular free Ca2+ in platelets which was counteracted by ketanserin. PGE1 and forskolin reduced the resting Ca2+-levels. 5HT did not affect either the basal or the PGE1-stimulated activity of adenylate cyclase, whereas the Ca2+-ionophore A23187 slightly raised the basal activity of the enzyme. In conclusion, the functional effects of 5HT2-receptor stimulation in human blood platelets (shape change reaction and enhancement of adrenaline aggregation) seem to be mediated by a rise of intracellular free Ca2+.This work was supported by the Swiss National Science Foundation as well as by the Alberto and Neni Bonizzi-Theler and the Emil Barell FoundationsPreliminary communications of some results presented here have been made at a satellite meeting (Shore Symposium) of the 5th International Catecholamine Symposium, Göteborg, 1983, and at the 3rd International Conference on Cyclic Nucleotides, Milano, 1983 相似文献
4.
Postnatal exposure of rats to lead has been shown previously to cause CNS hypo-myelination. Since rats intoxicated with lead often show retarded growth, the superimposed malnutrition, which as such can cause hypomyelination, may contribute to myelin deficit. In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1–15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation (Sundström et al. 1983). The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15–200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.Financed by grants from the Swedish Medical Research Council (project no 03488, 05249 and 07123), from the Swedish Worker Environment Fund (project no 81-0149), from the Medical Faculty, University of Göteborg, and from the Royal Society for Arts and Sciences of Göteborg 相似文献
5.
目的探讨脑出血(ICH)患者微创血肿清除手术后,患者血清髓鞘碱性蛋白(MBP)及血清胶质纤维酸性蛋白(GFAP)水平的变化。方法收集ICH患者58例,采用随机数字表法分为两组,其中微创组给予微创血肿清除手术治疗,保守组给予常规内科治疗,同时随机选取30例健康人作为对照组。微创组、保守组于治疗前、治疗后1d、3d、7d、14d,对照组于纳入该研究当天抽取静脉血检测血清MBP及GFAP。结果微创组治疗总有效率为96.6%(28/29),高于保守组的79.3%(23/29)(x2=4.06,P〈0.05)。MBP水平:微创组、保守组两组治疗前与对照组差异不明显;发病后1d,其水平开始升高,与治疗前比较差异有统计学意义;治疗后7d开始下降,保守组到14d后MBP水平仍高于治疗前;治疗期间,微创组不同时间MBP水平均明显低于保守组。GFAP水平:治疗前微创组、保守组两组患者GFAP水平已明显高于对照组;治疗后两组GFAP水平持续升高,直到14d下降,仅微创组接近于正常;治疗期间,微创组不同时间GFAP水平均明显低于保守组。结论微创血肿清除术治疗ICH有比较好的效果,且可以明显降低患者血清MBP及GFAP水平。 相似文献
6.
Summary Arginine-vasopressin (AVP) caused a marked shape change reaction and rise in [Ca2+]i in human blood platelets only when the extracellular buffer contained Mg2+ or Ca2+. At physiological concentrations of the cations the potency of AVP was higher in the presence of Mg2+ than of Ca2+. The amplitude of the shape change reaction was also greater with Mg2+ than with Ca2+, although the [Ca2+]i-rise was slightly more marked with extracellular Ca2+. The concentration of Mg2+ at which AVP showed half of its maximal effects was below the physiological plasma level of the cation, whereas the corresponding value for Ca2+ was higher. Addition of Ca2+ to the Mg2+ containing medium did not further enhance the action of AVP on platelet shape. In platelet-rich plasma the potency and efficacy of AVP in causing a shape change were similar in the presence and absence of EGTA, whereas with EDTA in the medium AVP had no effect. In conclusion, Mg2+ has an essential physiological role in AVP-induced platelet activation, which is brought about partly by release of intracellular calcium and partly by some other intracellular mechanism. 相似文献
7.
目的研究S100β、髓鞘碱性蛋白(MBP)含量的变化与糖尿病患者周围神经病变的关系及其意义。方法 60例糖尿病患者分为糖尿病无神经病变组(n=30)和糖尿病并发神经病变组(n=30),并纳入30例健康者作为健康对照组。上述研究对象血清中S100β、MBP含量以酶联免疫吸附法检测。结果糖尿病并发周围神经病变组血清S100β、MBP阳性率较健康对照组和无神经病变组均升高,差异有统计学意义(P<0.05)。结论血清MBP及S100β蛋白测定可能成为糖尿病周围神经病变的早期诊断和随访指标之一。 相似文献
8.
9.
目的 探讨溃疡性结肠炎(UC)患者C反应蛋白(CRP)的检测及临床意义.方法 检测57例UC患者及30例健康对照组外周血CRP水平及血小板计数(BPC),分析两者对临床病情程度的影响.结果 活动期组患者外周血CRP水平及BPC明显高于缓解期组(P<0.05),缓解期与健康对照组比较,差异无统计学意义(P>0.05);重度组患者外周血CRP水平及BPC明显高于中度组(P<0.05),中度组、重度组患者明显高于轻度组(P<0.05,P<0.01).结论 外周血CRP水平和BPC对判断UC活动性及其严重程度具有重要价值. 相似文献
10.
In rabbit platelets, bacterial endotoxin (lipopolysaccharide), at a concentration of 10−4 g/ml, inhibited the uptake of 3H-5HT by platelets, especially by the granule fraction. Reserpine, at a concentration of 10−7 g/ml, counteracted the uptake of 3H-5HT by platelets, especially by the granule fraction. 相似文献
11.
Conformational properties of the myelin basic protein epitope QKSQRSQDENPV (MBP74‐85) which can initiate experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis, were investigated by semiempirical methods. Energy calculations were carried out on the full MBP74‐85 autoantigen and the antagonist analog [Ala81]MBP74‐85. These studies have revealed a low energy cyclic conformation for MBP74‐85 which is characterized by an agonist motif comprising an interaction of the sidechains of Arg78 and Asp81 of MBP74‐85. Disruption of this agonist motif by removal of the residue 81 carboxylate, as in the antagonist [Ala81]MBP74‐85, invokes a compensatory rearrangement of the molecule resulting in interaction of the Arg78 sidechain with the sidechain of Glu82 together with Lys75. This antagonist motif, comprising guanidino, amino, and carboxylate groups, has been reproduced previously in semimimetic peptides having the general structure Ser‐Arg‐LINKER‐Glu‐NH2 (where LINKER = one or more residues of aminocaproic acid or isonipecotic acid), which have preferred conformations characterized by interaction of the carboxylate with both the guanidino and amino groups in a similar manner to the antagonist motif in [Ala81]MBP74‐85. However, in EAE assays these small semimimetics turned out to be partial agonists, i.e., molecules with structures between agonists and antagonists. These findings provide insight into the design of small molecule (orally active) autoantigen antagonists for the treatment of autoimmune diseases such as MS. Drug Dev. Res. 48:1–5, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
12.
目的:研究腺苷对血小板中肌醇磷脂和蛋白质磷酸化的影响.方法:在Mg~(2 )和/或Ca~(2 )存在下,用猪血小板膜与[γ-~(32)P]ATP在30℃下保温3 min,测定~(32)P掺入磷脂或蛋白质.结果:5′-氯-5′-脱氧腺苷减少磷脂酰肌醇-4-磷酸和磷脂酰肌醇-4,5-二磷酸的生成[IC_(50)分别为71和75(95%可信限分别为60-85和62-90)μmol·L~(-1)],抑制与ATP呈竞争性,并抑制pleckstrin(C激酶主要底物)和肌球蛋白轻链的磷酸化[IC_(50)分别为75和82(95%可信限分别为62·90和66-102)μmol·L~(-1)].结论:腺苷影响血小板中肌醇磷脂信使通路,这有助于阐明腺苷对血小板活化的抑制作用. 相似文献
13.
Marian Wielosz Mario Salmona Giovanni de Gaetano Silvio Garattini 《Naunyn-Schmiedeberg's archives of pharmacology》1976,296(1):59-65
Summary In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent K
m
values (0.25–2.0 M). While the apparent K
m
values were rather similar for human and rat platelets, V
max was about 5 times higher in rat than in human platelets.The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibition of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets.Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake. 相似文献
14.
The uptake of 2,5-dimethoxy-4-methylamphetamine (DOM, STP) into rabbit blood platelets and the effect of DOM on uptake and release of 5-hydroxytryptamine (5-HT) from platelets have been investigated. Tritium labeled DOM was taken up slightly against the concentration gradient. DOM in concentrations ranging from 5 × 10?5 to 1 × 10?3 M did not affect 14C-5-HT uptake into platelets. However, it increased the 14C-5-HT release from platelets by 100 and 300% at 2 × 10?4 and 1 × 10?3 M respectively when platelets were incubated in Krebs-Ringer phosphate buffer, but exerted no effect on the release of 14C-5-HT from the platelets when incubated in 0.9% saline. The mechanism and significance of the increase of 14C-5-HT release from platelets by DOM were discussed. 相似文献
15.
目的探讨高压氧治疗对中重型颅脑损伤后血糖和C-反应蛋白的影响。方法根据入院时首次GCS计分,符合人选标准的84例颅脑损伤患者中中型颅脑损伤(G1)44例、重型颅脑损伤(G2)40例,再分别随机将G1、G2组中的患者分为治疗组和对照组,治疗组给予常规治疗及高压氧治疗,对照组仅常规治疗。分别测定全部患者入院24小时内、高压氧治疗第一个疗程和高压氧治疗第二个疗程后的清晨血糖和C-反应蛋白值,并进行对比分析。结果颅脑损伤后空腹血糖和C-反应蛋白的增高与颅脑损伤程度均成正相关关系,且空腹血糖和C-反应蛋白两者之间也成正相关性。结论测定空腹血糖和C-反应蛋白有助于了解颅脑损伤的病情。高压氧治疗可以降低空腹血糖和C-反应蛋白。 相似文献
16.
Jouko Tuomisto 《Naunyn-Schmiedeberg's archives of pharmacology》1973,279(4):361-370
Summary The effect of 5-hydroxytryptamine (5-HT), tryptamine (T), 6-hydroxy-1,2,3,4-tetrahydroharmane (6-HTH), and 1,2,3,4-tetrahydroharmane (TH) on the accumulation of radioactive 5-HT and histamine, was studied in rabbit blood platelets. 6-HTH and TH inhibited the uptake of the labelled amine, but they were weaker inhibitors than 5-HT or T. All four compounds inhibited the accumulation of radioactive histamine in the granules as well as in the whole cells, but the latter effect is not the consequence of inhibition of granular accumulation.It is concluded that the methylene bridge, which is the most important structural difference between the harmanes and the tryptamines, does not abolish the affinity of the molecule to the uptake receptor at the platelet membrane. However, since the inhibitory potency was lower than that of the parent amines, one cannot be certain as to whether or not the conformation present in the harmane derivatives offers the best fit for the receptor. 相似文献
17.
目的分析C-反应蛋白(CRP)和血常规的临床检测功能和应用价值。方法抽取本院2012年1~6月处于急性感染期的患者105例作为观察组,择取同期健康者103例作为参照组,分别检测两组人员的CRP和血常规情况。结果观察组与参照组CRP阳性率分别为100.00%(105/105)、3.88%(4/103),差异有统计学意义(P〈0.01);观察组血常规检测中白细胞(WBC)总数与中性粒细胞增加有46例(43.81%),WBC总数正常、中性粒细胞增加有50例(47.62%),WBC总数与中性粒细胞均正常有9例(8.57%),总阳性率为91.43%,与参照组比较,差异有统计学意义(P〈0.01)。结论 CRP和血常规在临床的测定作用是相辅相成的,但CRP敏感度更高且更快捷,在临床应用上更具优势。 相似文献
18.
Burster T Marin-Esteban V Boehm BO Dunn S Rotzschke O Falk K Weber E Verhelst SH Kalbacher H Driessen C 《Biochemical pharmacology》2007,74(10):1514-1523
Multiple Sclerosis (MS) is considered to be a T cell-mediated autoimmune disease. An attractive strategy to prevent activation of autoaggressive T cells in MS, is the use of altered peptide ligands (APL), which bind to major histocompatibility complex class II (MHC II) molecules. To be of clinical use, APL must be capable of resisting hostile environments including the proteolytic machinery of antigen presenting cells (APC). The current design of APL relies on cost- and labour-intensive strategies. To overcome these major drawbacks, we used a deductive approach which involved modifying proteolytic cleavage sites in APL. Cleavage site-directed amino acid substitution of the autoantigen myelin basic protein (MBP) resulted in lysosomal protease-resistant, high-affinity binding peptides. In addition, these peptides mitigated T cell activation in a similar fashion as conventional APL. The strategy outlined allows the development of protease-resistant APL and provides a universal design strategy to improve peptide-based immunotherapeutics. 相似文献
19.
目的探讨阿托伐他汀(立普妥)对脑梗死及短暂性脑缺血发作患者C.反应蛋白(C-reactireprotein,CRP)及血脂的影响。方法将120例伴有颈动脉粥样硬化斑块的脑梗死及短暂性脑缺血发作患者随机分为治疗组与对照组;治疗组口服阿托伐他汀及抗血小板聚集等常规治疗,对照组仅予抗血小板聚集等常规治疗,于治疗前、治疗后3个月、治疗后6个月对血脂和C-反应蛋白进行检测比较治疗前后各指标的变化情况。结果使用阿托伐他汀治疗后患者血清C-反应蛋白、胆固醇、甘油三脂、低密度脂蛋白显著降低;高密度脂蛋白在治疗前后无统计学差异。结论阿托伐他汀可以有效降低LDL-C和TC水平,同时能够明显降低CRP的浓度。 相似文献
20.
Kempuraj D Tagen M Iliopoulou BP Clemons A Vasiadi M Boucher W House M Wolfberg A Theoharides TC 《British journal of pharmacology》2008,155(7):1076-1084