丝裂霉素纤维蛋白胶凝胶化疗的缓释特性

[目的]探讨丝裂霉素纤维蛋白胶凝胶( MMC/FG)化疗的缓释特性.[方法]体外释放实验中,将 8 mg 丝裂霉素( MMC)与 5 mL纤维蛋白胶( FG)混合成凝胶 MMC/FG,将凝胶置于 50 mL含纤溶酶原及尿激酶的磷酸盐缓冲液( PBS)中,在 37 ℃恒温摇床中培养.分别于开始培养 15 min, 2、 8、 24、 48、 72、 96、 120 h后取 0.1 mL PBS作样本,测试其中的 MMC质量浓度,观察 MMC的释放过程.体内实验中,将 MMC/FG(实验组)或单纯 MMC溶液(对照组)在开腹直视下注入小鼠肝脏,定时取小鼠肝脏及少量外周血作样本,测试样本中的 MMC质量浓度,计算肝脏及外周血中 MMC的动力学参数.[结果] 体外释放实验显示, 2 h后 MMC的累计释放率为 (33.91± 2.29)%, 24 h后为 (64.46± 3.18)%, 96 h后释放趋于平衡.动物实验显示,肝组织 MMC峰质量浓度(ρ max)两组差别无统计学意义( P >0.05),外周血ρ max实验组显著低于对照组( P< 0.01);肝组织及外周血 MMC的消除半衰期( t1/2)及曲线下面积( AUC)实验组均明显长于或大于对照组( P< 0.01).[结论] 在体内外条件下 MMC/FG均有良好的缓释性,在小鼠肝脏局部使用 MMC/FG,可延长 MMC在肝脏的滞留时间,降低其在外周血的质量浓度.     

胰岛素缓释载体聚乙二醇-聚己内酯-聚甲基丙烯酸-N,N-二乙氨基乙酯的制备及评价

目的 制备pH敏感聚乙二醇-聚己内酯-聚甲基丙烯酸-N,N-二乙氨基乙酯(mPEG-PCL-PDEAEMA)载胰岛素缓释纳米粒,考察其体外释放效果和体内降糖活性.方法 结合开环聚合反应和原子转移自由基聚合反应合成具有不同疏水链段的mPEG-PCL-PDEAEMA,用傅里叶红外光谱和核磁共振氢谱表征其结构;采用纳米沉淀技术制备聚合物载胰岛素纳米粒,动态光散射法测定粒径,透射电子显微镜观察其形态;BCA法测定载药情况,并考察其体外释放行为;建立糖尿病大鼠模型,监测给药后血糖水平.结果 在pH1.2~7.4时,聚合物纳米粒的粒径随pH增大而减小.以90%wt投药比制备mPEG5k-PCL13k-PDEAEMA10k和mPEG5k-PCL10k-PDEAEMA10k载胰岛素纳米粒时的包封率和载药率为最佳,包封率分别为(81.99±1.77)%和(53.12±0.62)%,载药率分别为(42.46±0.53)%和(32.34±0.26)%,粒径分别为181.9±6.67 nm和169±7.1 nm.体外释放结果显示聚合物载胰岛素纳米粒具有出色的缓释行为,并且随着疏水链段的增长,药物释放速度减慢.体内药效实验表明mPEG5k-PCL13k-PDEAEMA10k载胰岛素纳米粒能够在体内保持48 h的降血糖效果,较游离胰岛素的降糖作用时间明显延长.结论 pH敏感三嵌段聚合物mPEG-PCL-PDEAEMA有望成为理想的胰岛素缓释载体.     

纤维蛋白胶顺铂凝胶化疗的缓释特性

目的 探讨纤维蛋白胶顺铂凝胶化疗的缓释特性.方法 体内释放实验中,将顺铂和纤维蛋白胶混合成凝胶20例为实验组,单纯顺铂化疗20例为对照组,定时取少量外周血和尿液作样本,测试样本中顺铂浓度,计算外周血及尿液中顺铂的动力学参数.结果 体内实验显示,外周血顺铂峰浓度实验组和对照组分别为(192.2±33.5)μg/L、(1077.6±176.6)μg/L,实验组显著低于对照组(P<0.01);尿液顺铂峰浓度实验组和对照组分别为(18.6 4-8.7)μg/L、(55.8±12.7)μg/L,实验组显著低于对照组(P<0.01),外周血实验组的消除半衰期为23.32 h,而对照组为13.93 h,外周血及尿液中的顺铂消除半衰期及曲线下面积实验组均明显长于或大于对照组(P<0.01).结论 在体内条件下纤维蛋白胶顺铂凝胶具有良好的缓释性,在腹腔局部使用,可延长顺铂在腹腔的滞留时间,降低外周血的铂类浓度.

Abstract：

Objective To summarize the sustained dynamic release characteristics of fibrin glue enwrapping cisplatin.Methods In this in vivo study,20 patients received fibrin glue enwrapping cisplatin placed into the abdominal cavity while another 20 patients received cisplatin as the control group.Their peripheral blood and urine samples were collected at a regular interval to determine the concentrations and the pharmacokinetic parameters of cisplatin.Results The peak peripheral blood concentration of cisplatin in the study group was significantly lower than that in the control group[(192.2±33.5)vs(1077.6±176.6)μg/L,P<0.01].And the peak urine concentration of cisplatin Was significantly lower in the study group than that in the control group[(18.6±8.7)vs(55.8±12.7)μg/L,P<0.01].The elimination half-life of cisplatin was 23.32 h and 13.93 h respectively in the study and control groups.The elimination half-life and the area under the curve in peripheral blood and urine samples of the study group were significantly longer than those of the control group(P相似文献   

壳聚糖化疗药物缓释药粒局部治疗骨巨细胞瘤的实验研究

目的 :探讨骨巨细胞瘤化疗的可行性及确定生物可降解材料壳聚糖作为其治疗的药物载体的可能性。方法 :体外培养骨巨细胞瘤标本 ,测定药物及壳聚糖的敏感性 ;将壳聚糖与化疗药制成缓释药粒 ,进行体外及体内释放实验。结果 :骨巨细胞瘤对阿霉素 (ADM)、顺氨氯铂 (CDDP)中度敏感。单纯壳聚糖对骨巨细胞瘤在体外无抑制作用。体外及体内实验第 1天 ADM释放量较大 ,其后在较低水平维持相对稳定的缓慢释放达 8周以上。结论 :骨巨细胞瘤可以进行化疗 ,但只适合缓释药粒的局部治疗。壳聚糖与敏感化疗药物制成的缓释制剂的局部应用 ,具有局部浓度高、缓释时间长的优点。     

生物蛋白胶甲氨蝶呤缓释药粒在兔的体外和体内实验

目的：研究抗肿瘤药物载体的不同浓度纤维蛋白胶对抗肿瘤药物释放的影响.方法：（1）配制抗肿瘤药物与不同浓度纤维蛋白胶混合制剂.（2）纤维蛋白胶缓释药粒体外试验.（3）动物实验：把纤维蛋白胶甲氨蝶呤缓释药粒植入兔胫骨上端进行体内释放实验,并与静脉注射相同剂量甲氨蝶呤进行比较.结果：（1）纤维蛋白胶MTX缓释剂的药物释放与纤维蛋白浓度有关.体内外试验表明在释放初始时低及高纤维蛋白浓度组均有较高药物释放,后期药物释放量与纤维蛋白浓度呈负相关.（2）三组低、中、高不同浓度纤维蛋白胶缓释药粒,可使MTX在局部骨组织中维持有效含量达3周,中浓度组在第4周仍有较高有效含量.且骨组织中最高含量是静脉注射相同剂量时骨含量300倍以上,但血浆峰值浓度仅为静脉组血浆峰值七分之一以下.结论：（1）纤维蛋白胶体浓度变化不仅影响胶体密度,而且影响所含药物浓度.药物释放量与两者相互作用有关.（2）三种低、中、高不同浓度纤维蛋白胶体与MTX制成的缓释药粒具有良好的缓释功能.该缓释药粒MTX的1次局部用量可超过静脉注射1次用量的7倍以上,能较好的满足骨肿瘤局部化疗用药量大,维持时间较长,血浆药物浓度低,全身反应小的用药要求.（3）维持骨肿瘤局部较高的药物含量,及较长的时间宜选取用中等浓度的纤维蛋白胶体.     

苯扎贝特缓释微丸胶囊的研制及体内外评价

目的:研制苯扎贝特缓释微丸胶囊。方法:采用离心造粒技术制备苯扎贝特缓释微丸胶囊;以体外释药和犬的药代动力学参数进行评价。结果:微丸得率86.5%,载药量87.8%;体外释放曲线符合一级方程,相似因子f2为74.23;自制缓释微丸胶囊单剂量犬口服给药后的tmax(3.7±0.5)h,cmax(36.36±0.98)μg/mL,AUC0-∞(337.83±7.29)μg.h/mL;苯扎贝特缓释片(参比片)的tmax(4.1±0.4)h,cmax(39.66±0.94)μg/mL,AUC0-∞(327.27±8.97)μg.h/mL。结论:以进口的缓释片为参比片,自制的苯扎贝特缓释微丸胶囊具有良好的缓释作用;相对生物利用度为(103.3±2.8)%,两种制剂生物等效。     

医用生物蛋白胶携载更昔洛韦体外缓释研究

目的:建立HPLC测定体外类体环境中更昔洛韦浓度的方法,并考察医用生物蛋白胶携载更昔洛韦在体外的缓释作用.方法:用医用生物蛋白胶携栽更昔洛韦.观察缓释情况并测定其释放率.HPLC流动相为水:甲醇(2:98);流速:1 ml/min;检测波长:252 nm;柱温:30℃.结果:更昔洛韦在5～350 μg/ml范围内线性关系良好;日内和日间精密度RSD为O.89%～2.35%,高、中、低3个浓度的回收率为98.4%～100.8%.该方法灵敏度高,重复性好,可适用于在体外条件下更昔洛韦浓度的测定.结论:医用生物蛋白胶携栽更昔洛韦在体外类体环境下缓释效果良好.     

肺癌治疗缓释化疗药栓塞装置的研究

目的研制用于肺癌治疗的带缓释化疗药栓塞装置,通过体外、体内的释放实验评价其释放特性。方法用乙基纤维素、顺铂配成一定的比例,在带Ivalon泡沫海棉的镍-钛记忆合金支架上分次涂层自制栓塞装置,其中5个采用转篮法体外药物释放实验,了解其体外释放特性。采用萨能奶山羊(n=6),经介入方法把本装置置入于右下肺动脉,对照组(n=6)采用右下肺动脉灌注顺铂,两组术后均定时抽右下肺静脉血测顺铂浓度,明确其体内释放特性。结果体外释放观察时间为24 h,体外累计释放率>70%,在最初1 h内有突释效应。带药栓塞组1、2、8 h测得的肺静脉血药浓度均高于灌注组(P<0.05)。结论采用乙基纤维素作为缓释材料制作的带缓释顺铂栓塞装置在体外、动物体内均具有缓释作用,在体内有利于提高肺组织局部药物的浓度。     

不同浓度表皮生长因子对小鼠2-细胞胚胎体外发育的影响

目的:研究不同浓度表皮生长因子(ep iderm al growth factor,EGF)对ICR小鼠2-细胞胚胎体外发育的影响。方法:在mKSOM培养液中添加不同浓度(0.1,1.0,10和100 ng/m l)的EGF对小鼠2-细胞胚胎进行体外培养72 h、96 h,观察囊胚发育率、孵化率和胚胎细胞数的变化。结果:实验组加入四种不同浓度EGF胚胎培养72 h后,其囊胚率分别为93.8%、92.4%、91.8%、91.2%;96 h后其孵出率分别为61.1%、61.8%、63.0%、60.1%,均显著高于对照组(79.9%、43.1%,P<0.05),囊胚细胞数分别为73.1±13.4、73.8±7.0、74.3±12.2、77.6±8.2,与对照组(72.1±6.9)比较,差异无显著性(P>0.05);四个实验组间差异亦无显著性(P>0.05)。结论:EGF浓度在0.1,1.0,10和100 ng/m l范围内可提高体外培养鼠胚的囊胚率与孵出率;胚囊细胞数无变化;不同浓度EGF对早期鼠胚未见有毒性作用。     

阿司匹林壳聚糖缓释片的体外释放度研究

目的:研究阿司匹林壳聚糖缓释片的体外释放度。方法:以壳聚糖作为骨架材料制备阿司匹林缓释片并进行体外释放度实验。结果:自制阿司匹林壳聚糖缓释片在1h、2h、4h、6h、8h、10h的体外释放度为(18.60±0.88)%、(35.58±2.15)%、(60.22±1.07)%、(80.66±1.64)%、(98.53±1.15)%、(98.55±1.76)%。结论:药物的体外释放模型符合Higuchi方程。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.