三磷酸腺苷脂质体的研究

本文就提高脂质体的药物包裹率，对质备方法进行了研究，提出了新的制备方法---改良乳化法（IEV），是ATP脂质体的药物包过率达到38.9%,超过文献方法，此法在国内外尚未见报道。选用草果滤技术分离未包裹的药物，用辐射灭菌法达到灭菌。这些方法对脂质体的 工业化生产有潜在的实用价值。     

85例三磷酸腺苷不良反应分析

综述报道85例三磷酸腺苷所致的94例次不良反应的类型与特点，以老年组的不良反应发生率最高（占55．56％），不良反应类型中变态反应占40．43％，心血管反应占44．48％，死亡7．45％，其它反应7．45％。     

三磷酸腺苷的电药理效应

采用三磷酸腺苷（ATP）治疗阵发性室上性心动过速（PSVT）作用快，副作用小已有报道。为探讨其作用机理和作用部位，我们对2例PSVT患者作了电生理一电药理试验。1病例资料例1女，26岁。间歇性心悸10余年。心动过速发作时心室率达200次／min。体查无特殊，ECG诊断为A型预激综合征。例2女，24岁。因阵发性心动过速10余年，经食道调搏初诊为隐匿性左侧旁道参与的阵发性室上性心动过速入院。其它检查无器质性心脏病证据。心动过速发作时曾先后采用心律平、异搏定等药效果不佳，故而作电药理检查以选择有效抗心律失常药物。2方法学经皮经右…     

三磷酸腺苷和全静脉营养液的配伍稳定性考察

目的:考察三磷酸腺苷在全静脉营养液中的配伍稳定性。方法:将配好的混合药液在室温避光条件下放置24h,并在一定的时间点观察配伍液的外观性状,应用显微镜观察脂肪乳剂的粒径大小及形态变化,测定配伍液的pH值及渗透压,并用高效液相色谱法测定ATP的含量。结果:ATP加入全静脉营养液后24h内营养液的外观、pH值、渗透压无显著变化,脂肪乳剂的大小及分布与空白营养液差异无显著性,ATP的含量在90%以上。结论:24h内室温避光条件下ATP与全静脉营养液的配伍稳定。     

细胞内三磷酸腺苷和腺苷在细胞凋亡中的作用研究进展

众所周知,细胞内三磷酸腺苷(ATP)是维持细胞生命的重要能量物质,细胞内ATP缺失将导致细胞死亡[1]。近年的研究表明,ATP和腺苷还是细胞内外重要的信号分子,特别是在外周和神经系统中发挥着重要的作用[2]。此外,越来越多的研究表明,ATP和腺苷对神经系统、免疫系统以及内皮细胞和肿瘤细胞在内的多种细胞具有细胞毒作用[3],该作用主要是通过诱导细胞凋亡而实现。笔者近来的研究结果亦表明,ATP和腺苷对食管癌TE-13和胃癌HGC-27细胞具有抑制增殖、诱导凋亡的作用[4~6]。有关ATP和腺苷诱导细胞凋亡作用的研究目前多集中在嘌呤受体的介导…     

三磷酸腺苷治疗阵发性室上性心动过速

目的探讨三磷酸腺苷终止阵发性室上性心动过速的有效剂量及安全性和有效性。方法21例阵发性室上性心动过速患者,初始剂量5mg快速静脉推注,如无效逐渐递增至10mg,15mg,20mg。结果20例复律,1例未复律,不良反应轻微,均为一过性。结论三磷酸腺苷治疗阵发性室上性心动过速疗效好,安全性高。     

三磷酸腺苷临床应用10不宜

<正> 三磷酸腺苷(ATP)能改善机体代谢,参与体内脂肪、蛋白质、糖、核酸及核苷酸的代谢,同时又是体内能量的来源。然而,ATP 并非万能药,若用药指征掌握不严而滥用,也可导致不良反应而致命。有鉴于此,现结合有关文献提出ATP 临床应用10不宜,以供参考。有过敏史及支气管哮喘史者 ATP系生物制剂,可致过敏反应,特别是对     

三磷酸腺苷脂质体鼻用凝胶制备及其抗缺氧作用

制备三磷酸腺苷(adenosine triphosphate, ATP)脂质体,评价其对缺氧性脑损伤的治疗作用。采用离子对薄膜分散法制备ATP脂质体,其最优处方:三磷酸腺苷二钠、十六烷基三甲基溴化铵、大豆磷脂、胆固醇的质量比为1∶1.98∶8∶3,此时ATP脂质体包封率为(81.50±0.82)%,载药量为(6.79±0.07)%。通过体外释放实验与流变学测定分别考察ATP脂质体与空白凝胶的理化性质;将ATP脂质体、ATP水溶液分别加入甲基纤维素凝胶中,以甲基纤维素凝胶为阴性对照,进行小鼠鼻腔给药。动物实验获得军事医学研究院伦理委员会批准。连续给药9天后,与空白凝胶或ATP水凝胶相比, ATP脂质体水凝胶显著提高了血中红细胞与血红蛋白数值(P<0.01);连续给药13天后,在常压密闭缺氧实验中,与ATP水凝胶或空白凝胶相比, ATP脂质体鼻用凝胶能显著提高小鼠标准缺氧耐受时间(P<0.05)。小鼠海马促凋亡基因p53免疫组化染色显示, ATP脂质体对脑组织有明显保护作用。结果表明, ATP脂质体鼻用凝胶预防给药能明显提高小鼠耐缺氧能力,是一种前景广阔的抗缺氧制剂。     

应用固定化芽孢杆菌CPU—931105再生腺苷三磷酸

本文报道了用固定化含高活力乙酰激酶的芽孢杆菌菌体从ADP再生ATP的方法，采用明胶一戊二醛共价交联法，使菌体中降解ATP的酶受到抑制，而保持乙酰激酶的活力，使产物ATP得以积累，在柱式反应器中，ADP浓度为1mg/ml时，空间流速SV为0.5hr^-1，连续操作7天，再生ATP的转化率可维持在80%以上。     

三磷酸腺苷治疗阵发性室上性心动过速的疗效观察

目的:观察静脉注射三磷酸腺苷(adenosine triphosphate,ATP)终止阵发性室上性心动过速(paroxysmal supraventricular tachycardia,PSVT)的有效剂量和安全性,为基层医院的医生治疗PSVT推荐一种便于获取、疗效好、安全性高的治疗选择.方法:符合诊断的68例PSVT患者,常规刺激迷走神经治疗无效者,给予ATP0.10 mg/kg为起始剂量,以0.05 mg/kg为递增剂量,经肘静脉注射,直至PSVT终止或因症状较重不能忍受,单次使用最大剂量不超过0.25 mg/kg.结果:67例PSVT患者终止,所需ATP最小有效剂量为0.10mg/kg,最大剂量为0.25 mg/kg,所需ATP平均剂量为0.13 mg/kg;1例无效.患者普遍有乏力、头晕、面红、胸闷感,但均为一过性,患者能耐受,无晕厥等严重不良反应.结论:采用个体化给药,以0.15 mg/kg为起始剂量的ATP终止PSVT的有效率为82.35％,且无明显不良反应.故推荐基层医生首选ATP、采用以此剂量为起始的递增用药方法终止PSVT.     

Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: a calcium imaging study

Satellite glial cells (SGCs) in sensory ganglia are altered structurally and biochemically as a result of nerve injury. Whereas there is ample evidence that P2 purinergic receptors in central glial cells are altered after injury, there is very little information on similar changes in SGCs, although it is well established that SGCs are endowed with P2 receptors. Using calcium imaging, we characterized changes in P2 receptors in SGCs from mouse trigeminal ganglia in short-term cultures. Seven days after the induction of submandibular inflammation with complete Freund’s adjuvant, there was a marked increase in the sensitivity of SGCs to ATP, with the threshold of activation decreasing from 5 μM to 10 nM. A similar observation was made in the intact trigeminal ganglion after infra-orbital nerve axotomy. Using pharmacological tools, we investigated the receptor mechanisms underlying these changes in cultured SGCs. We found that in control tissues response to ATP was mediated by P2Y (metabotropic) receptors, whereas after inflammation the response was mediated predominantly by P2X (ionotropic) receptors. As the contribution of P2X1,3,6 receptors was excluded, and the sensitivity to a P2X7 agonist did not change after inflammation, it appears that after inflammation the responses to ATP are largely due to P2X2 and/or 5 receptors, with a possible contribution of P2X4 receptors. We conclude that inflammation induced a large increase in the sensitivity of SGCs to ATP, which involved a switch from P2Y to P2X receptors. We propose that the over 100-fold augmented sensitivity of SGCs to ATP after injury may contribute to chronic pain states.     

参附注射液对脑缺血再灌注损伤大鼠脑能量代谢的影响

目的 探讨参附注射液对脑缺血再灌注损伤大鼠的脑能量代谢的影响及其可能的机制.方法 ♂ SD大鼠30只,随机均分为空白对照组(C组)、脑缺血再灌注组(IR组)、参附注射液预处理组(SFI组).HPLC测定大鼠脑组织中的高能磷酸化合物三磷酸腺苷(ATP)的含量;应用乳酸及Na+-K+-ATPase检测试剂盒观察大鼠脑组织中乳酸及Na+-K+-ATPase的变化.结果 C组、IR组大鼠脑组织中乳酸含量为0.20±0.04、0.70±0.05 mmol·g-1;C组ATP的含量为416.81±20.52 ng·mL-1,Na+-K+-ATPase为5.98±0.53μmol· mg·h-1,而IR组大鼠脑组织中ATP的含量及Na+-K+-ATPase的活性均明显低于C组(P＜0.01),表明脑缺血再灌注损伤大鼠模型的建立成功;而给予SFI预处理后,SFI组大鼠脑组织中乳酸含量降低到0.42±0.04 mmol·g-1,明显低于IR组(P＜0.01),而ATP的含量及Na+-K+-ATPase活性则均较IR组明显升高(P＜0.01).结论 参附注射液预处理可以通过提高缺血再灌注大鼠脑组织中的ATP含量、增强Na+-K+-ATPase的活性,降低脑组织中乳酸的含量,以改善大鼠的脑缺血再灌注损伤.     

HPLC法测定术后疲劳综合征大鼠骨骼肌ATP,ADP,AMP的含量

目的:建立改良的高效液相色谱(HPLC)法测定术后疲劳综合征(POFS)大鼠骨骼肌5’-三磷酸腺苷(ATP)、5’-二磷酸腺苷(ADP)、5’-磷酸腺苷(AMP)的含量。方法:采用色谱柱Hypersil ODS2(4.6 mm×150 mm,5μm),柱温25℃;流动相为100 mmol.L-1磷酸盐缓冲液(含12 mmol.L-1的磷酸氢二钠和88 mmol.L-1的磷酸二氢钠,pH=6.5)-甲醇(99.9∶0.1,体积比);流速1.0 mL.min-1;紫外波长为254 nm;进样量20μL。结果:ATP、ADP、AMP色谱峰在10 min内得到了较好的分离,在测定范围内均呈良好的线性关系,r分别为1.000,0.9996,0.9994;精密度试验日内RSD≤4.1%,日间RSD≤3.5%;稳定性试验RSD≤4.8%;重复性试验RSD≤2.3%;回收率在97.1%～105.4%之间,RSD≤4.8%。应用改良的方法对模型组大鼠和对照组大鼠骨骼肌ATP、ADP、AMP的含量进行检测。结果显示,与对照组相比,模型组大鼠骨骼肌ATP含量在术后第1,3 d明显下降(P<0.05),ADP含量在术后第7 d明显升...     

Ketorolac entrapped in polymeric micelles: preparation, characterisation and ocular anti-inflammatory studies

Two types of ligand anchored multilamellar liposomes (MLVs) containing amphotericin B (Amp B) were prepared. The MLVs consisting of soya phosphatidylcholine (PC) and cholesterol (Chol) were coated with O-palmitoyl mannan (OPM). Similarly, the MLVs with the same Amp B content consisting of soya PC, Chol and phosphatidylethanolamine (PE) were prepared and covalently anchored with p-aminophenyl-mannopyranoside (PAM). The surface modified MLVs and their plain counterparts were characterised for size, shape, lamellarity, entrapment efficiency and ligand density. The stability in serum and in vivo bio-distribution in albino rats were also determined. It was observed that extent of accumulation of liposomal Amp B in macrophage rich organs, particularly liver, spleen and lungs was significantly high when compared against the free drug. The rates and extent of accumulation were found to increase further on ligand anchoring. In either of the cases, the macrophagic uptake of ligand anchored liposomes was inhibited significantly on pre-injection of hydrolysed mannan, being suggestive of receptor mediated uptake of ligand anchored liposomes. Comparison of biodistruibution pattern of ligand anchored MLVs revealed that PAM linked liposomes exhibited a higher hepato-splenic accumulation where as drug accumulation in lungs was highest in the case of OPM coated liposomes. It was thus observed that mannopyranoside is a specific ligand for targeting bioactives to the macrophages of liver and spleen while OPM could preferentially negotiate the targeting of bioactives to the alveolar macrophages.     

Adenosine triphosphate-induced gastric cytoprotection against ulcerogenic effects of hypothermic restraint stress and diclofenac in rats

The Protective effect of adenosine triphosphate (ATP) on gastric ulcer induced in rats has been studied. Gastric ulceration was induced by hypothermic restraint stress or diclofenac sodium. Gastric acid secretion and mucosal injury produced by the hypothermic restraint stress was greater as compared with those produced by diclofenac sodium. ATP significantly reduced area of injury, however, increased cyclic adenosine monophosphate (cATP) content. Administration of dipyridamole along with ATP did not change the total lesion area in both models when compared to ATP alone. Aminophylline antagonized the protective effect of ATP on the injured area. Farnotidine was found to be effective in reducing gastric acid output as well as the total injured area without any change in cAMP content when given along with ATP.     

The effects of electrical stimulation, adenosine and adenosine -5′ triphosphate (ATP) on mouse rectal muscle

The effects of electrical field stimulation and of purine compounds, adenosine and adenosine-5'-triphosphate (ATP) were examined on the mouse isolated rectum. Electrical field stimulation induced frequency-dependent contractions of mouse rectal muscles which were potentiated by physostigmine and inhibited by atropine or tetrodotoxin. Contractile amplitude at 37 degrees C was significantly (P less than 0.05) greater than at 25 degrees C, but the degree of potentiation by physostigmine was significantly (P less than 0.05) greater at 25 degrees C. ATP (1.6 x 10(-4)-1.28 x 10(-3) M) and adenosine (1.8 x 10(-4)-1.48 x 10(-3) M) inhibited in concentration-related fashion contractile responses induced by KCl (1.34 x 10(-2) M-1.07 x 10(-1) M) by acetylcholine (2.2 x 10(-7) M-1.4 x 10(-5) M) and by CaCl2 in high KCl (120 mM)-CaCl2-free Tyrode solution. Theophylline and quinidine ('purinoceptor' antagonists) antagonized ACH contractile effects and so could not be satisfactorily employed in the characterization of the purine receptors in the mouse rectum. It may be concluded from this study that in the mouse rectum, acetylcholine is an excitatory neurotransmitter and that there is a non-adrenergic, non-cholinergic inhibitory neuromuscular transmission in this tissue. Further, ATP and adenosine have been demonstrated to cause relaxation in this tissue by possibly a post-synaptic mechanism involving inhibition of Ca2+ influx into the depolarized muscle.     

Preparation,characterization and biodistribution of nanostructured lipid carriers for parenteral delivery of bifendate

Nanostructured lipid carrier (NLC)-loaded bifendate (DDB) was prepared by melt-emulsification method to improve drug payloads and liver targeting. The particle size of the prepared formulation analysed by photon correlation spectroscopy (PCS) was 217.4?nm with a narrow polydispersity index (PI) lower than 0.2, meanwhile the loading capacity increased from 4.3% to 15.7% in comparison with DDB-loaded SLN reported in previous study. The zeta potential value was ?21.91?mV, and transmission electron microscopy studies revealed NLC of irregularly spherical shape. With respect to lipid polymorphism, a less ordered structure of NLC was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, tissue distribution of DDB-loaded NLC and DDB solution were carried out in Kunming strain mice. In tested organs, the distribution of DDB-loaded NLC to liver was higher than that of free drug. These results support the potential applications of NLC for the delivery of DDB.     

Reactivity of guinea-pig Isolated trachea to methacholine, histamine and isoproterenol applied serosally versus mucosally

Guinea-pig tracheas were perfused with recirculating modified Krebs-Henseleit solution while monitoring changes in inflow-outflow pressure difference, which is an index of trachealis muscle tone. The reactivities of the trachealis muscle to methacholine, histamine and isoproterenol applied separately to the mucosal (intraluminal, IL) or serosal (extraluminal, EL) compartments were compared, and evidence for the agonist-induced release of epithelium-derived relaxing factor (EpDRF) was sought. All agents were more potent when added to the EL compartment, but the IL/EL EC₅₀ ratios were different: 100 for methacholine, 41 for histamine and 25 for isoproterenol. Methacholine or histamine added to the IL compartment, after the preparations were pre-contracted with the same concentration of the agonist or 30 mM KCl added EL, did not result in relaxation. Likewise, IL isoproterenol did not evoke contraction. IL KCl evoked relaxation. The results indicate that the epithelium reduces access of bronchoactive agents to the muscle, while an immediate relaxant effect of EpDRF released by agonists could not be demonstrated.