我院48例血栓通冻干粉所致不良反应分析

目的分析医院血栓通冻干粉所致药品不良反应情况,探讨其发生的可能因素,为临床合理用药提供参考。方法对2007年至2010年收集的48例与血栓通冻干粉相关的药品不良反应进行分析。结果大于60岁的老年人药品不良反应发生率较高(56.25%),用药1～7 d后出现药品不良反应的比例较高(43.75%)。药品不良反应常以皮疹、瘙痒为主的过敏反应,其次为发热、寒颤、多汗的全身性损害及消化道反应。结论医务人员应正确使用药品,密切关注患者用药过程中的情况;制药企业应加强研发,生产合格有效产品,并重视上市后的安全性再评价工作,以保证用药安全。     

流感疫苗脂质体干粉黏膜免疫研究

目的考察H3N2单价流感疫苗脂质体诱发呼吸道黏膜免疫的效果,并比较呼吸道不同部位产生抗体水平的差异。方法将实验小鼠分为非脂质体疫苗原液组、脂质体疫苗冻干粉组、阳性对照和阴性对照组（n=5）。非脂质体疫苗原液组和脂质体疫苗冻干粉组各以每只4μg和6μg血凝素含量（H3N2亚型）滴鼻免疫,同时以非脂质体疫苗原液腹腔给药和脂质体疫苗冻干粉腹腔给药作为阳性对照,以未免疫小鼠（磷酸盐缓冲液给药）作为阴性对照。免疫28 d后,采用间接ELISA法检测血清IgG和呼吸道黏膜sIgA分泌水平。结果脂质体滴鼻给药诱导的黏膜sIgA水平高于腹腔给药免疫组（P〈0.05）,上呼吸道（鼻咽部）黏膜sIgA水平明显高于下呼吸道（肺部）（P〈0.01）;与非脂质体组滴鼻免疫相比,上呼吸道脂质体组诱发的sIgA水平较低（P〈0.01）,而下呼吸道脂质体组诱发的sIgA水平较高（P〈0.05）。结论流感疫苗脂质体滴鼻给药能有效诱发体液免疫和呼吸道黏膜免疫,上呼吸道黏膜免疫水平高于下呼吸道,但与非脂质体相比,脂质体在下呼吸道（肺部）能表现出更好的免疫佐剂效应。     

炙甘草汤加味联合冻干重组人脑利钠肽治疗慢性心力衰竭68例

目的:观察炙甘草汤加味联合冻干重组人脑利钠肽治疗慢性心力衰竭的临床疗效。方法:将136例慢性心力衰竭患者按照随机数字表法分为对照组和观察组,每组各68例。对照组予以冻干重组人脑利钠肽治疗,观察组在对照组的基础上联合炙甘草汤加味治疗。比较两组患者治疗前后左心室功能[左心室舒张末期内径(left ventricle end diastolic diameter,LVEDD)、左心室收缩末期内径(left ventricular end systolic diameter,LVESD)及左心室射血分数(left ventricular ejection fraction,LVEF)]、血清基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、人心型脂肪酸结合蛋白(human heart type fatty acid binding protein,H-FABP)水平、24 h平均心率、6分钟步行距离以及健康调查简表(short from health survey,SF-36)评分的变化情况。结果:两组患者治疗后LVEDD...     

Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation,optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging

To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3¹4¹ full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788?nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps’ nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery.     

Comparative study of lyophilized human dura mater and lyophilized bovine pericardium as dural substitutes in neurosurgery

Summary In a prospective, controlled randomized study either lyophilized bovine pericardium or lyophilized human dura mater have been used as a patch for the closure of the dura in 102 patients. The aim of this investigation was to compare both materials in terms of immunogenic response of the patients. The rate of post-operative complications was comparably low in both groups (wound infection in 1/51 patients each). In regard of workability, thicknesss of the material and flexibility the pericardium patches were judged to be by far superior. Neither signs of a cellular nor of an intesified humoral response could be detected in patients who received the pericardium implants. Thus, lyophilized bovine pericardium seems to be a superior alternative for the surgical repair of dural defects.     

Ultrastructural comparison of the morphology of three different platelet and fibrin fiber preparations

The aim of the current study was to investigate the ultrastructural morphology of three different sources of fibrin networks and platelets, namely, lypholized human platelet‐rich plasma (LPRP), freshly prepared human platelet‐rich plasma (FPRP), and human platelet concentrate (HPC). The ultrastructural morphology of the three different fibrin networks was studied using the scanning electron microscope (SEM). Turbidity curves were drawn at 405 nm at room temperature and fibrinogen concentrations were measured. Scanning electron micrographs showed that all clots produced thick major fibrin fibers as well as a well‐defined fine fibrin network, which appeared to be a superimposed process that occurred after the major fibrin network was established. These features were decidedly more pronounced in the HPC specimens. Turbidity curves of the three types of plasma showed differences in LPRP and FPRP. Fibrinogen concentrations of all three preparations were in the normal ranges. Because of the great similarity between LPRP, HPC, and FPRP, we suggest that LPRP could be used successfully to study morphological changes in fibrin fibers and platelets, which may occur after exposure to certain therapeutic agents. However, functionality studies such as turbidity curves should concurrently be included. We therefore conclude that from a basic science point of view, LPRP is a valuable research tool and that such results may add information that could be valuable for clinical application. Anat Rec 290:188–198, 2007. © 2007 Wiley‐Liss, Inc.     

氧化苦参碱磷脂复合物固体脂质纳米粒冻干粉的制备与质量评价

目的：制备氧化苦参碱磷脂复合物固体脂质纳米粒（OMT-PC-SLN）冻干粉,并对其进行药剂学性质评价。方法：采用伪三元相图优选微乳处方;以包封率为指标,采用单因素试验优选OMT-PC-SLN冻干粉的处方工艺;利用透射电子显微镜（TEM）观察该制剂的外观形态,激光粒度仪测定粒径,并考察OMT-PC-SLN冻干粉的体外释药性能。结果：最佳处方工艺为大豆磷脂和15-羟基硬脂酸聚乙二醇酯（Kolliphor HS 15）为乳化剂,乙醇为助乳化剂,乳化剂与助乳化剂的比例（K_m）=3∶2,油相∶（乳化剂+助乳化剂）=1∶9,氧化苦参碱磷脂复合物-硬脂酸-大豆磷脂-Kolliphor HS 15-乙醇（30∶100∶180∶360∶360）;含4%甘露醇的水50 mL为外水相,1000 r·min^-1冰浴搅拌固化1 h,于-20℃预冻24 h,取出,干燥24 h。OMT-PC-SLN冻干粉外观呈类球形,包封率（38.09±1.24）%,平均粒径785.5 nm,多分散系数（PDI）0.456,Zeta电位-24.82 mV;体外释放结果表明OMT-PC-SLN冻干粉2 h时累积释放率72.63%,12 h累积释放率98.42%,原料药在2 h的累积释放率98.60%。结论：优选的OMT-PC-SLN冻干粉处方工艺稳定、重复性好;与原料药相比,OMT-PC-SLN冻干粉体外释放较慢,具有一定的缓释效果。     

Concomitant administration of a liquid formulation of human rotavirus vaccine (porcine circovirus-free) with routine childhood vaccines in infants in the United States: Results from a phase 3, randomized trial

BackgroundIn response to the detection of porcine circovirus type 1 (PCV-1) in the human rotavirus vaccine (HRV), a PCV-free HRV (no detection of PCV-1 and PCV-2 according to the detection limit of tests used) was developed. Liquid (Liq) PCV-free HRV previously showed immunogenicity and safety profiles comparable to lyophilized (Lyo) HRV.MethodsThis was a phase 3a, randomized, single-blind study (NCT03207750) conducted in the United States. Healthy infants aged 6–12 weeks received 2 doses (0, 2 months) of either Liq PCV-free HRV or Lyo HRV with routine vaccines (0, 2, 4 months): diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus combination vaccine (DTaP-HBV-IPV), monovalent tetanus toxoid-conjugated vaccine against Haemophilus influenzae type b (Hib-TT), and 13-valent pneumococcal conjugate vaccine. Co-primary objectives were: (i) to assess non-inferiority of immune responses to routine vaccine antigens 1 month post-dose 3 following co-administration with Liq PCV-free HRV compared to Lyo HRV; (ii) to rule out a 10% decrease in seroresponse to pertussis antigens after dose 3. Other objectives were to evaluate immunogenicity and safety of HRV vaccines.ResultsOf 1272 vaccinated infants, 990 (489 in Liq PCV-free HRV and 501 in Lyo HRV group) were included in the per-protocol set. All statistical criteria were met, thus co-primary objectives were demonstrated. Seroprotection/seropositivity rates in both groups were high: 100% for diphtheria/tetanus, ≥99.3% for HBV, ≥99.8% for polio, ≥99.8% for each pertussis antigen, ≥90.8% for all pneumococcal serotypes except serotype 3 (≥69.1%), and ≥ 97.4% for Hib. Most infants seroconverted for anti-RV antibodies (76.3% of Liq PCV-free HRV and 78.9% of Lyo HRV recipients). Geometric mean concentrations/titers were comparable between groups. Incidences of adverse events and serious adverse events were similar between groups.ConclusionRoutine pediatric vaccines co-administered with Liq PCV-free HRV showed non-inferior immune responses and similar safety profiles to those following co-administration with Lyo HRV.     

国产冻干麻疹、流行性腮腺炎二联减毒活疫苗的临床反应和血清学免疫效果研究

为了观察我国首次研制的冻干麻疹、流行性腮腺炎(腮腺炎)二联减毒活疫苗的反应性和血清学免疫效果,1998～1999年在江西省选麻疹、腮腺炎抗体均阴性的≥8月龄婴儿接种该疫苗,以分别接种腮腺炎疫苗、麻疹疫苗和进口麻疹、腮腺炎、风疹联合疫苗(MMR)的婴儿为比较和对照.用微量中和试验、血凝抑制试验分别检测腮腺炎和麻疹抗体.结果显示136名婴儿接种麻疹、腮腺炎二联疫苗后,未发生腮腺肿大和皮疹,发热反应多为弱反应(15.44%),中反应5.88%,无强反应.腮腺炎抗体阳转率为81.82%～86.00%,抗体几何平均滴度(GMT)为13.88～16.79,与接种腮腺炎疫苗者相似;麻疹抗体阳转率为95.12%～100%,抗体GMT为163.79～l76.11,与接种麻疹疫苗者相似.与MMR的抗体水平也基本一致.这说明该疫苗反应性小,免疫效果好,可以推广应用.