Factors affecting aerosol performance during nebulization with jet and ultrasonic nebulizers

Nebulization of aqueous solutions is a convenient delivery system to deliver drugs to the lungs because it can produce droplets small enough to reach the alveolar region. However, the droplet size might be affected by the changes in the temperature and the concentration of the nebulizing solution in the reservoir during nebulization. In this study, the changes in the droplet size over the nebulization time using a PariBoy air-jet and a Multisonic ultrasonic nebulizer have been studied. The findings were related to changes in the temperature, concentration, surface tension, viscosity and saturated vapour pressure of the nebulizing solution. By using the jet nebulizer, an increase in the droplet size followed by a decrease has been observed. This observation could be attributed to the approx. 7 degrees C reduction of the temperature during the first 2 min in the jet nebulizer reservoir which increased the viscosity of the nebulizing solution. After this initial period of time, the increasing drug concentration induced a reduction of the surface tension and, consequently, a decrease in the droplet size. However, with the ultrasonic nebulizer a temperature increase of approx. 20 degrees C during the first 6 min in the nebulizing solution was observed leading to a decrease in droplet size, viscosity and surface tension and an increasing saturated vapour pressure. This again led to smaller average droplet sizes.     

Drug release from reservoir pellets compacted with some excipients of different physical properties

The aim of the present study was to investigate the influence of the size and the porosity of excipient microcrystalline cellulose (MCC) particles on the densification and the deformation during compaction and the consequent effect on the drug release from reservoir pellets. Drug pellets consisting of salicylic acid and microcrystalline cellulose were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Excipient pellets of different size and porosity were prepared by extrusion-spheronisation or direct spheronisation. Five binary mixtures of reservoir pellets and excipient particles were prepared in the proportion 1:7 and lubricated. After compaction the reservoir pellets were retrieved and analysed to determine the intragranular porosity, surface area, shape and drug release. The reservoir pellets were shown to undergo extensive deformation and densification during compaction, resulting in a preserved or even prolonged drug release time. The mode of deformation of the reservoir pellets seems to be critical for the compression-induced change in drug release. Formation of large indents has a negative effect on the release time, while the use of small particles or small deformable agglomerates has a protective effect. We also hypothesize that the coating structure changes during compaction and the final structure of the coating is the net effect of two parallel processes, one reducing and one prolonging the drug transport time across the coating.     

IL-12协同B7-1诱导机体抗肿瘤免疫的实验研究

目的研究白细胞介素-12(Interleukin-12,IL-12)协同共刺激分子B7-1,联合诱导机体抗肿瘤免疫对大鼠卵巢上皮癌的治疗作用并探讨其机理.方法用携带有小鼠IL-12和B7-1的逆转录病毒表达载体感染大鼠卵巢癌细胞株NuTu-19,建立高表达细胞株NuTu-19/IL-12、NuTu-19/B7-1及双基因共表达细胞株NuTu-19/IL-12-B7-1,并以转染空载体pLXSN的细胞NuTu-19/Neo为对照.用经丝裂霉素C处理的各种基因修饰的肿瘤细胞免疫动物,观察卵巢癌腹腔转移模型动物生存期,及其诱导细胞毒性T淋巴细胞(cytotoxic lymphocyte,CTL)杀伤活性的作用.结果经各种基因修饰的肿瘤细胞免疫后,大鼠脾淋巴细胞增殖能力有不同程度的提高,CTL杀伤同源肿瘤细胞的活性明显增强,IL-12和B7-1基因联合修饰的肿瘤细胞免疫动物对模型动物生存期的延长具有显著意义(P＜0.05).结论IL-12和B7-1基因联合修饰的肿瘤细胞可以刺激机体CTL增殖、成熟,增强CTL对肿瘤细胞的识别和杀伤活性等,两者联合具有明显的协同效应.联合免疫基因治疗作为一种新的卵巢癌治疗方法,值得深入研究.     

人PTPRK基因在上皮性卵巢肿瘤中的表达及其意义

目的探讨受体型蛋白酪氨酸磷酸酶(PTPRK)基因在良性、交界性和恶性上皮性卵巢肿瘤及正常卵巢上皮组织中的表达规律及其与卵巢癌的关系.方法应用免疫组化间接法检测50例卵巢癌、13例良性上皮性卵巢肿瘤、14例交界性上皮性卵巢肿瘤及10例正常卵巢上皮组织中PTPRK基因的表达,采用Kaplan-Meier生存分析比较卵巢癌患者PTPRK蛋白表达与五年生存率的关系.结果(1)良性、交界性上皮性卵巢肿瘤和卵巢癌组中,PTPRK基因的阳性表达率分别为53.9%、57.1%、18.0%,显著低于正常卵巢上皮组的表达率100%(P均＜0.001).卵巢癌组中PTPRK基因的阳性表达率显著低于良性上皮性卵巢肿瘤组(P＜0.001)和交界性上皮性卵巢肿瘤组(P＜0.01).(2)卵巢癌高分化组中PTPRK基因的表达率为62.5%,显著高于中分化组(18.8%)和低分化组(6.3%)(P＜0.01).卵巢癌淋巴结无转移组PTPRK基因的表达率为27.3%,显著高于无阳性表达的淋巴结有转移组(P＜0.05).(3)PTPRK基因表达阳性组与表达阴性组的5年生存率分别为66.7%、46.7%,两组比较,差异无显著性(P＞0.05).结论PTPRK基因表达缺失发生在上皮性卵巢肿瘤组织中,肿瘤分化程度越低或者淋巴结已有转移则该基因表达缺失越明显.PTPRK基因可能是一种肿瘤抑制基因,其不同程度的表达缺失与上皮性卵巢肿瘤的发生和发展有关.     

反义LRP寡核苷酸对卵巢癌多药耐药细胞系OVCAR-3顺铂耐药性的影响

目的:探讨针对肺耐药基因(LRP gene)设计的反义寡核苷酸(AsODN)对人卵巢癌多药耐药细胞系OVCAR-3顺铂(DDP)耐药性的逆转作用.方法:采用罗丹明B(SRB)显色法检测LRP AsODN和DDP细胞毒性作用;采用脂质体(1iplfectamine 2000)介导LRP AsODN转染人卵巢癌多药耐药细胞系OVCAR-3;采用逆转录酶链式反应(RT-PCR)和Westem blot法检测LRP AsODN转染前后OVCAR-3细胞中LRP的表达:采用流式细胞仪测定OVCAR-3细胞在顺铂作用后的凋亡率.结果:LRP AsODN浓度低于800nmol/L时,对OVCAR-3细胞无明显细胞毒作用;LRP AsODN能明显减少OVCAR-3细胞中LRP mRNA和蛋白的表达,增加其顺铂敏感性,且与剂量呈正相关;转染LRP AsODN前后的OVCAR-3细胞在DDP作用后,凋亡率分别为(15.43±1.14)%和(27.43±2.05)%,两者间差异有显著性意义(p=0.001).结论:LRP AsODN能有效阻断OVCAR-3细胞内LRP的表达,恢复细胞对DDP的敏感性.     

非小细胞肺癌淋巴结大小与转移的关系

目的:评估非小细胞肺癌淋巴结大小与转移的相关性.方法:从形态测量学角度,分析258例非小细胞肺癌患者纵隔和肺门的淋巴结.记录每例淋巴结数目、最大径及病理结果.计算转移频数与淋巴结大小的相关性.回顾性分析其中80例患者术前CT扫描的淋巴结所见,与组织病理学诊断相对照.结果:检查258例标本的2 892枚淋巴结.140例患者为pN0期,118例为淋巴结阳性.2 487枚淋巴结(86.0%)无转移,405枚淋巴结(14.0%)有转移.无转移淋巴结平均直径是(7.05±3.7)mm,转移淋巴结是(10.7±4.7)mm,(P＜0.005).1 954枚无转移淋巴结(78.5%)和180枚转移淋巴结(44.3%)直径＜10mm.140例无转移淋巴结的患者中,102例(72.9%)至少有一枚淋巴结＞10mm118例转移患者中,13.0%淋巴结＜10mm.80例CT扫描评估的敏感性是57.0%,特异性80.2%结论:淋巴结大小不能作为评估非小细胞肺癌转移浸润的可靠参数.     

上皮性卵巢癌患者血清sICAM-1检测的意义

 目的　探讨血清可溶性细胞间粘着分子 1(sICAM 1)在上皮性卵巢癌中的临床意义。方法　利用ELISA法检测血清sICAM 1浓度。结果　卵巢上皮癌患者血清sICAM 1平均浓度和阳性率与良性卵巢瘤组和正常对照组相比有显著性差异 (P <0 .0 0 1) ;II～Ⅳ期显著高于临床Ⅰ期的患者 ;淋巴结转移阳性显著高于淋巴结转移阴性的患者 ;组织分化程度Ⅲ级者高于Ⅰ、Ⅱ级 (P <0 .0 1)。结论　血清sICAM 1检测可能有助于监测上皮性卵巢癌患者的病情和判断预后     

丁酸钠诱导卵巢癌3AO细胞凋亡的研究

 目的　探讨丁酸钠 (NaB)诱导卵巢癌细胞株 3AO凋亡的机制。方法　以不同浓度的NaB对体外培养的 3AO细胞进行作用 ,通过光镜和DNA琼脂糖凝胶电泳观察凋亡发生与药物剂量和作用时间的关系 ,进而选取 4mmol/LNaB作用 72h的 3AO细胞为实验组 ,应用流式细胞技术分析Fas/FasL、bcl 2 /Bax表达和线粒体跨膜电位的变化 ,透射电镜观察内质网形态的变化。结果　 4mmol/LNaB作用72h ,光镜下可见 3AO细胞出现凋亡改变 ,DNA琼脂糖凝胶电泳中出现典型的DNAladder,线粒体跨膜电位降低 ,内质网肿胀 ,bcl 2表达降低 ,Bax表达升高 ,而Fas/FasL无明显改变。结论　NaB可能通过线粒体通路和内质网通路诱导 3AO细胞凋亡 ,bcl 2 /Bax起着重要的调控作用。     

卵巢癌细胞DNA倍体、p21及p53基因表达产物定量分析

目的　探讨卵巢癌DNA倍体、p2 1及 p5 3基因定量表达情况及其临床意义。 方法　应用流式细胞术 (FCM )和荧光免疫技术 ,对 3 9例卵巢癌组织的卵巢癌细胞和 9例正常卵巢组织的卵巢细胞的染色体倍体、p2 1基因和 p5 3基因表达产物进行定量分析。结果　在卵巢癌组织中DNA的异倍体率、p2 1、p5 3基因蛋白产物的阳性表达率均明显高于对照组 ,两者比较均有非常显著性差异 (P <0 .0 1)。结论　应用FCM定量测定卵巢癌细胞中的DNA倍体、p2 1及 p5 3基因表达产物 ,在临床上具有重要的参考价值     

全反式维甲酸诱导人卵巢癌细胞凋亡的实验研究

目的：观察全反式维甲酸(A11一trans retinoic acid，ATRA)诱导人卵巢癌细胞CAOV3产生凋亡。方法：应用扫描电镜、透射电镜、DNA断裂分析及流式细胞术观察ATRA诱导人卵巢癌细胞CAOV3凋亡。结果：ATRA作用后电镜下细胞逐渐变圆，细胞表面微绒毛消失，核染色质更加致密，浓缩分块，胞质中有空泡形成，细胞表面出泡，脱落形成膜包裹的凋亡小体。流式细胞术不同浓度ATRA对CAOV3细胞凋亡作用的结果显示在DNA直方图上均出现低于G1期二倍体DNA含量的亚二倍体峰，随药物浓度增加，亚二倍体细胞从10^-8mol／L ATRA时的18．7％增加到10^-6mol／L的37．4％；10^-6mol／LATRA作用24h即诱导CAOV3细胞产生典型的梯形DNA条带(DNAlallder)，大小约180bp的整数倍递增，随ATRA作用时间延长而逐渐加强；结论：ATRA可以诱导卵巢癌细胞产生细胞凋亡，呈时间和浓度依赖性。