生长抑素临床应用研究进展

生长抑素是一种典型的脑肠肽,广泛分布于全身及胃肠道各组织器官中,具有抑制生长激素分泌,抑制胃酸、胃蛋白酶释放的功能,能减少内脏血流,并能减少胰腺的内、外分泌以及胃小肠和胆囊的分泌,对胰腺细胞具有保护作用的多肽类激素。本文就SS及其在临床应用的研究现状作一综述。     

肝细胞癌的病毒性乙型肝炎基础与甲胎蛋白的表达分析

为了探索肝细胞癌(HCC)与病毒性乙型肝炎(乙肝)的关系以及临床中甲胎蛋白(AFP)的表达,了解乙肝患者的治疗状况,阐明乙肝病毒(HBV)对人体的危害,呼吁人们对乙肝的重视,做到早诊断、早治疗,从而达到降低HCC的发病率。我院对1990年3月至2000年12月的300例HCC病人作总结。     

大剂量生长抑素治疗顽固性食管静脉曲张破裂出血

目的观察大剂量生长抑素治疗顽固性食管静脉曲张破裂出血的临床疗效。方法选择经常规剂量生长抑素治疗6 h仍出血不止的89例食管静脉曲张破裂出血的患者,随机分为2组。对照组(n=45):继续采用常规剂量生长抑素(250μg/h)静脉微量泵泵入维持注射;治疗组(n=44):采用大剂量生长抑素(500μg/h)静脉微量泵泵入维持注射,连用5 d。结果治疗组有效率86.36%,对照组有效率62.22%,两组比较,差异有统计学意义(P<0.05);两组患者1周内再出血率:治疗组(11.36%)低于对照组(15.56%),但两组比较,差异无统计学意义(P>0.05)。结论对顽固性食管静脉曲张破裂大出血患者,常规剂量生长抑素治疗效果不佳时加大剂量,治疗效果显著提高。     

生长抑素在小肠出血治疗中的应用

小肠出血是常见的内科急症之一 ,属下消化道出血 ,在诊治上较上消化道出血困难。 1996年 3月至 1999年 6月 ,我们应用生长抑素施他宁Ｓｔｉｌ ａｍｉｎ) ,治疗不明原因小肠出血 7例 ,与抗纤止血芳酸、止血敏、垂体后叶素等一般止血药组治疗的 5例病人相比较 ,疗效较为显著 ,现报道如下。临床资料　施他宁治疗组 7例 ,男性 5例 ,女性 2例 ,年龄 31～ 56岁 ,7例均有黑便、暗红色血便 ,个别还有呕血 ,4例便血时伴有腹部隐痛 ,中上腹部深轻压痛 ,肠鸣音亢进 ,另 3例无明显伴随症状。 5例病人伴有失血性休克表现 ,估计出血量≥ 10 0 0ｍｌ有 3例 …     

甲胎蛋白异质体在肝细胞癌中临床应用

目的评价甲胎蛋白异质体（AFP-L3）在肝细胞癌（HCC）中的临床应用。方法收集本院2011年8月至2012年4月住院、门诊患者及健康体检者血清,检测血清中AFP总含量,再应用微量离心柱法分离检测AFP-L3的百分含量。结果以AFP-L3〉10%作为阳性判断标准,68例肝癌患者血清AFP-L3阳性率为75.0%,45例肝硬化患者血清AFP-L3阳性率为2.2%,51例慢性肝炎患者血清AFP-L3阳性率为5.9%,60例体检者血清AFP-L3阳性率为0,肝癌患者AFP-L3水平明显高于肝硬化,慢性肝炎及健康人群（P〈0.01）。结论 AFP-L3是肝细胞癌鉴别诊断的有用指标,且与AFP联合检测更有利于肝细胞癌的诊断。     

生长抑素联合大承气汤治疗肠梗阻的疗效观察

目的 探讨生长抑素联合大承气汤治疗肠梗阻的疗效。方法 68例肠梗阻患者,按照入院编号随机分为观察组和对照组,各34例,对照组患者入院之后给予患者生长抑素治疗,观察组在对照组治疗的基础上采用大承气汤治疗,两组患者在接受为期1周的治疗后,比较治疗效果。结果 治疗前,两组患者一般资料对比差异无统计学意义(P>0.05)。治疗结束后观察组胃肠压量为(765±12)ml/d,对照组为(468±16)ml/d,组间治疗效果比较,差异有统计学意义(P<0.05)。结论 临床上在治疗肠梗阻时,可以采用生长激素联合大承气汤治疗方法 ,能有效改善患者治疗效果,提高预后质量,获得非常理想的治疗效果,值得在临床上大力推广。     

生长抑素在肠梗阻非手术治疗中早期应用的临床观察

目的 探讨生长抑素(丽枝雪南京长澳制药有限公司研制)在肠梗阻非手术早期治疗中的作用.方法 将收治的42例肠梗阻患者分为丽枝雪治疗组(22例)和常规治疗对照组(20例).对照组给予基础疗法,即禁食、胃肠减压、纠正水电解质紊乱和酸碱失衡、全胃肠外营养以及应用抗生素.治疗组除上述基础疗法外,并应用生长抑素(丽枝雪)6mg加入...     

生长抑素与大承气汤联合治疗肠梗阻112例疗效研究

目的探讨生长抑素与大承气汤联合治疗肠梗阻的疗效。方法 112例我院收治的肠梗阻患者,采用随机分级法将全部患者平均分为治疗组和对照组各56例。所有患者同时给予持续胃肠减压,常规禁食水、补液、纠正水电解质紊乱、联合应用抗生素及胃肠外营养。对照组在此基础上给予生长抑素治疗;治疗组在对照组的基础上给予大承气汤灌肠治疗。比较两组患者的治疗效果。结果治疗组56例患者中痊愈48例,占85.7%,好转3例占5.4%,无效5例,占8.9%,总有效率达到91.1%;对照组56例患者中痊愈40例,占71.4%,好转3例占5.4%,无效13例,占23.2%,总有效率达为76.8%。两组患者在治疗效果的比较上,治疗组患者的总有效率明显高于对照组的总有效率,两组结果差异具有统计学意义(P<0.05)。结论生长抑素与大承气汤联合治疗肠梗阻,可以有效治疗患者的肠梗阻,值得临床推广。     

生长抑素及其类似物治疗原发性肝癌的研究进展

生长抑素(somatostatin，SST)及其类似物抗肿瘤的分子生物学机制得到越来越深入的研究，也越来越广泛的应用于肿瘤的治疗。该类药物最早应用于神经内分泌肿瘤，现已广泛应用于实体性肿瘤，如肾癌，乳腺癌，小细胞肺癌，胰腺癌，胃癌等本文将近年来国内外生长抑素及其类似物在治疗原发性肝癌中的研究进展做一综述。     

对减少一般杂质检查法中试剂用量的探讨

《中国药典》2010年版附录收载的一般杂质检查法中,氯化物检查法、硫酸盐检查法、铁盐检查法、铵盐检查法所用的纳氏比色管均规定为50mL,方法沿用多年,未曾改进,检查过程中用到的试剂有的价格比较昂贵,如硝酸银;有的腐蚀性强,如稀硝酸、稀盐酸;有的毒性大,如氯化钡试液;这些试液对环境都有较大污染。我国现在已经进入环境污染治理期,作为药品检验工作者,应该在方法的建立或改进时考虑环境因素。本文以氯化物检查法、硫酸盐检查法为例,通过理论探讨与实验验证,在不改变方法原理、不影响质量控制的前提下,用特制比色管代替50mL纳氏比色管,可以大大减少试剂消耗量,节约检验成本,减少环境污染源。     

Kinetics and Mechanism of Degradation of a Cyclic Hexapeptide (Somatostatin Analogue) in Aqueous Solution

A highly active cyclic hexapeptide analogue of somatostatin, Cyclo(N-Me-L-Ala-L-Tyr-D-Trp-L-Lys-L-Val-L-Phe), L-363,586, was found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The compound is reported to be relatively stable in blood, nasal cavity, and intestinal lumen but undergoes rapid degradation in aqueous solution. The objective of this study was to elucidate the degradation mechanisms based on the kinetic data and the structure of the degradation products. Both pH and temperature had a profound influence on the instability of the peptide in aqueous solution. The data indicated that the peptide was most stable at a pH of about 4.7. The pH-rate profile exhibited specific acid catalysis at a pH less than 3.0 and base catalysis above pH 10.5. The kinetic pK _a was determined to be 9.7. This pK _a could be attributed to the tyrosine residue. The mechanisms of degradation under acidic and alkaline conditions appear to be different. Identification of the fragments obtained using mass spectrometry and amino acid sequencing suggest that the cyclic compound was cleaved to yield a linear fragment, which underwent further cleavage at both peptide linkages alpha to the trypto-phanyl residue. The indole group of that residue is probably the potential nucleophile attacking the adjacent carbonyls. A rate equation for the degradation of the hexapeptide has been proposed.     

Hepatic Uptake of Octreotide,a Long-Acting Somatostatin Analogue,via a Bile Acid Transport System

The hepatic transport mechanism of octreotide (Sandostatin^®), a somatostatin analogue, was studied using freshly prepared rat hepatocytes. The initial uptake rate of octreotide represented exclusively a saturable transport process. The half-saturation constant, K_t, and the maximum uptake-rate, J_max, for the uptake of octreotide were 91.1 ± 28.4 µM and 104.6 ± 19.7 pmol/mg protein/min, respectively. An energy requirement was demonstrated for [¹⁴C]octreotide uptake since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly reduced the initial uptake rate. [¹⁴C]octreotide uptake was also significantly inhibited by ouabain. [¹⁴C]octreotide uptake was reduced in the absence of Na⁺ in the uptake medium. [¹⁴C]octreotide uptake was significantly inhibited by bile acids, iodipamide, d-tubocurarine, whereas it was not inhibited by bilirubin, TEMA and insulin. Competitive inhibition of taurocholic acid was observed for octreotide uptake with the inhibition constant, K_i, of 82 ± 17 µM. Moreover, a significant inhibitory effect of octreotide was observed for the Na ⁺ dependent uptake of [¹⁴C]taurocholic acid. These results suggest that octreotide is transported into hepatocytes via a bile acid carrier-mediated system.     

Quantification and Visualization of the Transport of Octreotide,a Somatostatin Analogue,Across Monolayers of Cerebrovascular Endothelial Cells

Confocal laser scanning microscopy (CLSM) was used to quantify and visualize the transport of the octapeptide and somatostatin analogue, octreotide (SMS 201-995, Sandostatin), across monolayers of bovine cerebrovascular endothelial cells, an in vitro model of the blood–brain barrier. The concentrations of octreotide and its conjugates in the cell culture medium were determined by radioimmunoassay (RIA). Two fluorescent conjugates of octreotide (FITC- and NBD-octreotide) were used to obtain CLSM images. The peptides did not undergo significant degradation in the presence of brain endothelial cell monolayers. The transport rate of octreotide expressed as clearance (Cl) and endothelial permeability (P _e) did not depend on either the initial concentration (between 10 nM and 1 µM) or the site of administration (luminal or abluminal side of the mono-layer), indicating the absence of saturable and/or asymmetrical transport mechanisms. The P _e of octreotide and that of the paracellular permeability marker fluorescein correlated well. Although the conjugates are more lipophilic than octreotide itself, they exhibited lower Cl and P _e, values probably because of their larger molecular size. On the CLSM images, FITC-octreotide was present only in the intercellular space, while the cells did not exhibit detectable fluorescence. Transport studies and CLSM images suggest that octreotide passes the endothelial monolayer primarily via the paracellular route without significant contribution of carrier-mediated transport.     

Poly(alkyl cyanoacrylate) Nanocapsules as a Delivery System in the Rat for Octreotide,a Long-acting Somatostatin Analogue

Poly(alkyl cyanoacrylate) nanocapsules have been used as biodegradable polymeric drug carriers for subcutaneous and peroral delivery of octreotide, a long-acting somatostatin analogue; their ability to reduce insulin secretion or prolactin secretion in response to oestrogens has been studied in adult male rats. The nanocapsules, prepared by interfacial emulsion polymerization of isobutyl cyanoacrylate, were 260 nm in diameter and incorporated 60% of octreotide. Administered subcutaneously, the octreotide-loaded (20 μg kg^?) nanocapsules suppressed the insulinaemia peak induced by intravenous glucose overload and depressed insulin secretion over 48 h, preventing the secretory rebound; however, glycaemia was unaffected. In parallel, the plasma octreotide concentration increased 2.7 times. Administered perorally to oestrogen-treated rats, octreotide-loaded nanocapsules (200 and 1000 μg kg^?) significantly improved the reduction of prolactin secretion (by 72 and 88%, respectively, compared with 32 and 54% with free octreotide) and slightly increased plasma octreotide level. Thus nanocapsules could be of interest as a biodegradable drug carrier for the administration of octreotide.     

顺铂不同剂量联合长春瑞滨治疗非小细胞肺癌的临床研究

目的:对比研究顺铂(DDP)不同剂量联合长春瑞滨(NVB)在非小细胞肺癌(NSCLC)患者化疗中的疗效和不良反应。方法:123例Ⅲ～Ⅳ期NSCLC患者,采用不同剂量DDP联合长春瑞滨进行分组对照研究,分为低剂量DDP组(n=67)与高剂量DDP组(n=56)。低剂量DDP组给予NVB25mg.m-2,静脉滴注,第1、8天;DDP20mg.m-2,静脉滴注,第1～5天。高剂量DDP组给予NVB25mg.m-2,静脉滴注,第1、8天;DDP60mg.m-2,静脉滴注,第1～2天。21d为一周期。化疗2周期后评定疗效。结果:高剂量DDP组与低剂量DDP组的有效率分别为41.1%、28.4%(P>0.05);高剂量DDP组白细胞减少总发生率为87.5%,明显高于低剂量DDP组的71.6%(P<0.05);2组Ⅲ～Ⅳ度白细胞减少发生率无显著性差异(P>0.05)。结论:DDP高剂量组与低剂量组的临床疗效相当。高剂量顺铂组毒性反应的发生率显著高于低剂量组,但严重毒性反应的发生率相近。     

药物与辅料相容性研究进展

目的对药物与辅料的相容性及相互作用机制和研究方法进展作概述和分析。方法结合近年来国内外相关文献进行评述和展望。结果药物与辅料的相互作用可改变药物活性分子的理化性质,影响药物的稳定性和有效性。结论药物与辅料的相容性研究对制剂处方设计、提高制剂质量和安全性至关重要,药物与辅料相容性及作用机制研究的方法有热分析法、光谱法、色谱法等,可根据试验目的和要求选择适宜的分析方法。     

临床药师实施干预措施对降低苯二氮类药用量的效果评估

目的:评估临床药师实施干预措施对降低苯二氮类药用量的效果。方法:临床药师为重复应用苯二氮类药3个月以上的成年患者制订撤药方案,以每2周减量10%的梯度法减量,并予以单盲撤药。结果:临床药师实施干预措施后,苯二氮类药用量明显下降,平均下降率为70.50%。结论:临床药师在苯二氮类药撤药过程中起了关键作用,其干预措施是帮助医师降低患者苯二氮类药用量的快速、有效方法。     

9家肿瘤专科医院2012年镇痛药应用单次剂量及给药频次分析

目的：评价全国9家肿瘤专科医院2012年镇痛药单次剂量及给药频次,为临床合理用药提供参考。方法：采用回顾性方法,对全国9家肿瘤专科医院2012年镇痛药的应用数据进行统计、分析。结果：对9家医院常用15种镇痛药单次用药剂量的统计结果表明,多数镇痛药的单次用量符合说明书推荐用量,仅布桂嗪口服制剂和哌替啶口服制剂超过说明书推荐剂量比例在50%以上。对21种镇痛药给药频次的统计结果表明,多数镇痛药的给药频次符合说明书推荐,仅羟考酮/对乙酰氨基酚、双氢可待因/对乙酰氨基酚、地佐辛给药频次不符比例在30%以上。结论：镇痛药物单次用量和给药频次多数符合说明书规定,也存在个别不合理现象,需引起临床注意。临床医师应用镇痛药时应合理选择药物剂量和给药频次,做好用药监测,使更多患者得到更规范、有效的治疗。     

The Effect of Three Different Ranitidine Dosage Regimens on Reducing Gastric Acidity and Volume in Ambulatory Surgical Patients

Study Objective . To evaluate three different preoperative oral dosing regimens of ranitidine in ambulatory patients who had significant risk of aspiration pneumonitis (gastric pH ≤ 2.5 or volume ≥ 25 ml at intubation or extubation). Design . Double-blind, placebo-controlled, randomized trial. Setting . St. Francis Hospital of Buffalo, New York. Patients . Two hundred seventy-one ambulatory patients about to undergo a surgical procedure under general anesthesia, of whom 241 (89%) completed the trial and were considered evaluable. Interventions . Patients were randomly assigned to receive one of four regimens administered orally before surgery: placebo at bedtime the night before and in the morning on the day of surgery; ranitidine 150 mg at bedtime and in the morning; ranitidine 150 mg at bedtime and placebo in the morning; or ranitidine 300 mg at bedtime and placebo in the morning. Measurements and Main Results . Patients who received ranitidine 150 mg twice/day ranitidine 150 mg at bedtime, or ranitidine 300 mg at bedtime had a significantly (p<0.05) lower frequency of a gastric pH 2.5 or below at intubation or extubation than those taking placebo twice/day (3%, 45%, and 31%, respectively, vs 86%). In addition, gastric volume at intubation or extubation was 25 ml or above in significantly fewer patients receiving ranitidine 150 mg at bedtime than placebo (37% vs 13%, p<0.05). Overall, the number of patients with risk factors for aspiration pneumonitis was significantly lower with ranitidine 150 mg twice/day (20%), ranitidine 150 mg at bedtime (48%), and ranitidine 300 mg at bedtime (35%) than placebo (86%) (p<0.001), and significantly lower with ranitidine 150 mg twice/day than ranitidine 150 mg at bedtime (p<0.05). Conclusions . Ranitidine 150 mg twice/day preoperatively reduced to the greatest degree the percentage of patients who developed significant risk factors for aspiration pneumonitis after surgery under general anesthesia.