转移及复发性骨肿瘤的放射性125I粒子植入治疗初探

目的探讨放射性^125I粒子组织间种植治疗转移及复发性骨肿瘤的技术方法和疗效。方法对14例转移及复发性骨肿瘤患者行肿瘤内^125I粒子植入治疗，粒子植入数目为3～145颗，粒子活度为18．5～29．6MBq（0．5～0．8mCi），肿瘤匹配周边剂量为115～145Gy。术后行质量验证并观察患者临床指标改善情况。结果随访7～29个月（平均12．4个月）。^125I粒子治疗90％肿瘤靶体积接受的最小剂量（D90）中位值为108．12Gy（27～166Gy），10例脊柱或椎旁肿瘤患者脊髓的中位D90为31．9Gy（6．2～74．0Gy）。粒子植入前伴有疼痛的12例患者，术后疼痛完全缓解率达82％，止痛有效率为92％。10例脊柱或椎旁肿瘤患者中，70％的患者疗后行走能力改善或恢复正常。1年局部控制率为82％，1年生存率为53％，围手术期无3级以上严重并发症发生。结论放射性^125I粒子植入安全、高效，是治疗转移及复发性骨肿瘤的一种有前途的新方法。     

Characterisation and stability studies of a hydrophilic decapeptide in different adjuvant drug delivery systems: a comparative study of PLGA nanoparticles versus chitosan-dextran sulphate microparticles versus DOTAP-liposomes

Poly[lactic-co-glycolide] (PLGA) nanoparticles, chitosan-dextran sulphate microparticles, and DOTAP-liposomes were prepared as vaccine adjuvants and drug carriers for a small hydrophilic model peptide, and their different physico-chemical properties (size, PDI, zeta-potential, pH-value and peptide loading) were investigated. The model peptide's encapsulation efficiency (EE) in PLGA particles amounted to 15%, for DOTAP-liposomes to 20% and for chitosan particles up to 90%. The structural appearance of the particles was visualized by SEM and TEM. The stability of the aqueous formulations and the corresponding lyophilisates was monitored for 12 weeks (stored at T = 2-8 °C). The freeze-drying process and the addition of an appropriate cryoprotective agent (sucrose) proved to be essential for all carrier systems. As a result of this study, three different peptide-loaded drug delivery systems with different properties were successfully manufactured and showed sufficient product stability of their freeze-dried formulations over 12 weeks of storage.     

尿毒清颗粒治疗慢性肾功能衰竭的临床研究

目的观察口服尿毒清颗粒治疗慢性肾功能衰竭（CRF）患者的临床疗效。方法将100例患者随机分为两组各50例,分别进行常规治疗和加服尿毒清颗粒进行治疗。结果加服尿毒清颗粒治疗后患者肾小球滤过率（Ccr）明显升高,血肌酐（Scr）和尿素氮（BUN）明显下降（P〈0.05）。常规治疗组患者Ccr明显下降,而Scr、BUN明显升高（P〈0.05）,差异有统计学意义（P〈0.05）。结论尿毒清颗粒对降低CRF患者Cr、BUN水平,改善患者临床症状有明显疗效。     

痛经宁颗粒对原发性痛经患者血清肥大细胞脱颗粒及血清皮质醇含量的影响

目的:探讨中药痛经宁颗粒对原发性痛经(PD)患者焦虑症(HAMA)分值、抑郁症(HAMD)分值与血清肥大细胞(MC)脱颗粒类胰蛋白酶(MCT)及血清皮质醇(CS)含量的相关影响。方法:收集72例原发性痛经患者,随机分为中药组、西药组,均治疗1个疗程,并以18例正常者为对照。观察治疗前、后各组患者血清HAMA、HAMD分值与MCT、CS含量的变化。结果:原发性痛经患者HAMA、HAMD分值及血清MCT、CS含量显著高于正常组(P<0.05)。治疗后,中药组HAMA、HAMD积分值、血清MCT、CS含量显著降低,并低于西药组治疗后(P<0.05),西药组有下降趋势,但并无统计学意义。结论:PD患者存在焦虑、紧张、抑郁状态且与血清MC高表达、CS高水平呈正相关趋势。中药痛经宁颗粒调节精神情绪、降低血清中CS含量,减轻MC细胞脱颗粒,缓节应激等作用显著优于西药阿司匹林。     

小儿抗病毒颗粒药效学研究

目的观察小儿抗病毒颗粒的解热祛痰、镇咳平喘作用。方法采用干酵母致热造模法观察小儿抗病毒颗粒对大鼠的解热作用,给药剂量分别为4.18、2.09、1.05 g/kg,每天ig给药1次,连续3 d,末次给药后sc干酵母混合溶液,4～8 h后测大鼠体温。采用酚红比色法观察其对小鼠的祛痰作用,给药剂量分别为5.22、2.61、1.31 g/kg,每天ig给药2次,连续7 d,末次给药1 h后进行检测。采用氨水吸入引咳法观察其对小鼠的镇咳作用,给药剂量同祛痰实验,每天ig给药2次,连续3 d,观察潜伏期和咳嗽次数。采用雾化乙酰胆碱吸入引喘法进行豚鼠平喘试验,给药剂量分别为3.65、1.83、0.914 g/kg,每天给药2次,连续3 d,测定引喘潜伏期。结果小儿抗病毒颗粒能使小鼠气管酚红的分泌量增加(P<0.05);显著抑制由干酵母引发的大鼠发热反应(P<0.05)及小鼠的咳嗽潜伏期延长(P<0.05);使豚鼠哮喘潜伏期显著延长(P<0.05)。结论小儿抗病毒颗粒具有明显的解热祛痰、镇咳平喘作用。     

Modeling of occupational exposure to accidentally released manufactured nanomaterials in a production facility and calculation of internal doses by inhalation

Background: Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system.

Objectives: To estimate the occupational exposure and effective internal doses in a real production facility of TiO₂ MNMs during hypothetical scenarios of accidental release.

Methods: Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in-house software to calculate internal doses in the human respiratory tract by inhalation.

Results: Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source.

Conclusions: Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials.     

HIV-Gag VLPs presenting trimeric HIV-1 gp140 spikes constitutively expressed in stable double transfected insect cell line

We have previously described the establishment and characterization of a stably transfected insect cell line for the constitutive and efficient expression of Pr55 HIV Gag proteins, which auto-assemble into enveloped Virus-Like Particles (VLPs) released into the cell culture supernatant. Such HIV-Gag VLPs have been shown to elicit a specific systemic humoral response in vivo, proving the appropriate antigenic presentation of the HIV Gag protein to the immune system. Here we describe the establishment of a stable double transfected insect cell line for the constitutive and reproducible production of Pr55Gag-VLPs expressing on their surface trimeric forms of HIV-1 envelope glycoproteins. The persistence of HIV coding genes has been verified in clonal resistant insect cells, the protein expression and conformation has been verified by Western blot analysis. The resulting HIV-VLPs have been visualized by standard transmission electron microscopy and their immunogenicity has been evaluated in vivo. This represents, to our knowledge, the first example of stable double transfected insect cell line for the constitutive production of enveloped HIV-Gag VLPs presenting trimeric HIV-gp140 on their surface.     

Distribution of Phospholipids and Triglycerides in Multivesicular Lipid Particles

The distribution of phospholipid and triglyceride molecules in themembranes forming the nonconcentric vesicular network within a multivesicular lipid particle (MLP) and its precursors was investigated. MLP formulations afford controlled release of encapsulated pharmaceuticals over a time period ranging from a few days to a few weeks. The formation of MLP requires the use of a double emulsification process and a neutral lipid such as a triglyceride. MLP formulations with the antineoplastic agent cytarabine encapsulated in the aqueous compartments were prepared that further contained [13C]carbonyl-enriched triolein, and quantitative 13C nuclear magnetic resonance (NMR) experiments were performed to quantitate membrane-soluble and bulk triglyceride. In the NMR spectra of MLP, components attributable to triolein residing in a location similar to that of bilayer phospholipid were not observed. Spectral components attributable to triolein in a liquid-like phase were observed, and the intensity of these components accounted for the triolein present in the sample. Laser scanning confocal microscopy with two phospholipid fluorescent probes, RhodamineDHPE and NBD-PG, and a triglyceride fluorescent probe, BodipyTriglyceride, was used to visualize the distribution of the lipid components in the emulsion precursors of MLP and in MLP themselves with cytarabine, amikacin, morphine, or sucrose encapsulated within the aqueous phases. The confocal micrographs revealed a uniform distribution of the two phospholipid probes in the plane of the membrane, whereas the triglyceride probe accumulated at discrete locations. The NMR and microscopy results are consistent with a structural model for MLP in which triolein acts as a hydrophobic space filler at bilayer intersection points and stabilizes these junctions, and is also present as oil droplets dispersed in the encapsulated aqueous compartments. The experimental approach presented here could provide a rational approach to the development of MLP formulations with variable rates of sustained release, modulated by changes in the distribution of various phospholipids and triglycerides.     

尿素酶三甲基壳聚糖亚微球的制备及其相关性质的初步研究

目的 制备尿素酶三甲基壳聚糖亚微球,并对其相关性质进行初步研究.方法 采用离子交联法制备尿素酶三甲基壳聚糖亚微球,激光纳米粒度仪测量粒度分布、多分散性和Zeta电位,透射电镜观察粒子的形态,比色法测定酶活性以间接测定包封率,并考察主要影响因素.结果 所制备的尿素酶三甲基壳聚糖亚微球形态规则,粒径分布均匀,平均粒径为303.0nm,多分散系数(PDI)=0.175,Zeta电位为18.1 mV;包封率为89.69%.结论 采用离子交联法可制备粒度分布均匀、形态规则、具有较高包封率的尿素酶三甲基壳聚糖亚微球.     

Indoor air particles and bioaerosols before and after renovation of moisture-damaged buildings: the effect on biological activity and microbial flora

Many building-related health problems coincide with moisture damage and mold growth within a building. Their elimination is assumed to improve indoor air quality. The aim of this study was to follow the success of remediation in two individual buildings by analyzing the microbial flora and immunotoxicological activity of filter samples. We compare results from samples collected from indoor air in the moisture-damaged buildings before and after renovation and results from matched reference buildings and outdoor air. The microbial characteristics of the samples were studied by analyzing ergosterol content and determining the composition of fungal flora with quantitative polymerase chain reaction (QPCR). In addition, the concentrations of particles were monitored with optical particle counter (OPC). The immunotoxicological activity of collected particle samples was tested by exposing mouse macrophages (RAW264.7) for 24 h to particle suspension extracted from the filters, and measuring the viability of the exposed cells (MTT-test) and production of inflammatory mediators (nitric oxide, IL-6 and TNFα) in cell culture medium by enzyme-linked immunoassay (ELISA). The results show that for Location 1 the renovation decreased the immunotoxicological activity of the particles collected from damaged building, whereas no difference was detected in the corresponding samples collected from the reference building. Interestingly, only slight differences were seen in the concentration of fungi. In the Location 2, a decrease was seen in the concentration of fungi after the renovation, whereas no effect on the immunotoxicological responses was detected. In this case, the immunotoxicological responses to the indoor air samples were almost identical to those caused by the samples from outdoor air. This indicates that the effects of remediation on the indoor air quality may not necessarily be readily measurable either with microbial or toxicological parameters. This may be associated with different spectrum of harmful agents in different mold and moisture-damaged buildings.