软胶囊崩解迟缓现象影响因素研究

目的：研究储存条件以及软胶囊处方对明胶胶片稳定性的影响，探讨软胶囊崩解迟缓的原因。方法：制备明胶胶片模拟软胶囊囊壳，采用溶胀动力学法测定明胶胶片平衡溶胀量(Seq)，同时测定软胶囊内容物溶媒PEG400中甲醛含量。以上述结果为指标，考察不同储存条件与胶囊处方对明胶胶片交联程度的影响。结果：空白明胶胶片在40℃条件下Seq与对照组具有极显著性差异，PEG400中甲醛含量增加。含有甘油、山梨醇、二氧化钛等辅料的胶片浸泡在PEG400中后Seq与对照组具有极显著性差异，PEG400中甲醛含量量著增加。加速条件下含有抗氧剂的胶片Seq与PEG400中甲醛含量变化不大。结论：在考察的储存条件中，温度对软胶囊稳定性影响较大。含有一些常用辅料的明胶胶片易受PEG400中外源性醛类杂质的影响，Seq降低。低沮保存、纯化辅料以及添加抗氧剂有助于缓解软胶囊崩解迟缓现象的发生。     

ANALYSIS OF BURIED BUMPER SYNDROME AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY DUE TO USE OF A BUTTON‐TYPE KIT

Background: Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Along with the widespread use of the button‐type kit, BBS is encountered frequently. Methods: In the present study, we examined causes and treatments for BBS among 1400 patients who had undergone PEG. Results: The causes of BBS after PEG were classified into two categories: early causes consisted of wound infection, inappropriate size of kit and severe lordosis, while late causes were inappropriate exchange of kit, rough management or weight gain. The treatments for BBS could be determined by the degree of wound infection, fistula and burial of the bumper. Conclusion: We prepared a flowchart for replacement, by which BBS can be managed safely and quickly without surgical or endoscopic intervention.     

两性霉素B/聚乙二醇-聚谷氨酸苄酯纳米球溶血毒性的研究

目的:考察两性霉素B/聚乙二醇-聚谷氨酸(AmB/PEG-PBLG)纳米球是否能降低AmB的溶血毒性.方法:超微透析法制备AmB/PEG-PBLG纳米药球,用紫外分光光度法测定样品的溶血率.结果:AmB/PEG-PBLG纳米药球平均粒径142.1 nm,载药量27.55%;溶血率从低到高依次为:PEG-PBLG空白纳米球、脱氧胆酸钠、AmB/PEG-PBLG纳米药球、AmB注射液.结论:AmB/PEG-PBLG纳米药球能有效降低AmB的溶血毒性.     

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants.

Interpenetrating polymer networks (IPNs) of poly(acrylamide-co-ethylene glycol/acrylic acid) [p(AAm-co-EG/AAc)] functionalized with an -Arg-Gly-Asp- containing peptide derived from rat bone sialoprotein [bsp-RGD(15)] were grafted to titanium implants in an effort to modulate osteoblast behavior in vitro. Surface characterization data were consistent with the presence of an IPN, and ligand density measurements established that the range of peptide density on the modified implants spanned three orders of magnitude (0.01-20 pmol/cm2). In vitro biological characterization of the modified implants employing the primary rat calvarial osteoblast (RCO) model resulted in the identification of a critical ligand density (0.01相似文献   

A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C

Overall treatment results of chronic hepatitis C have improved markedly with the introduction of pegylated interferon-alpha (PEG–IFN-) and ribavirin combination therapy. However, cure rates in the most common genotype 1 infection are still unsatisfactory. IFN- dose–response studies on viral kinetics suggest that inadequate dosing might be a key factor but drug levels have hardly been tested, which is in part due to difficulties in measuring this cytokine in patient samples. We have shown recently that hepatitis C virus (HCV) replicons are highly sensitive to IFN-. In this report we tested whether the replicon system could be used as a sensitive bioassay to determine the amount of biologically active IFN- in serum or heparinized plasma of patients under therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA was developed that carries the gene encoding the firefly luciferase. Dose response studies with IFN- demonstrate that the amount of expressed luciferase directly correlates with the level of HCV replication. By using this cell-based assay, serum samples of HCV patients treated with different types and doses of IFN- were analyzed in parallel to IFN- standards made by serial dilutions of the same type of IFN- the patient was treated with. Based on nonlinear logistic models serum concentrations corresponding to 1.3–19 U/ml were determined in patients under standard or high dose IFN- therapy, and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-. In conclusion, the HCV-replicon based bioassay allows determining the levels of biologically active IFN- in serum and heparinized plasma of patients under treatment.     

Characterization of two epitopes on insulin using monoclonal antibodies

Three monoclonal antibodies (MAb), 21 (IgG1), I10 (IgG1) and H38 (IgG2b), to insulin have been tested for cross-reactivity with 11 species variants of insulin and three of proinsulin. Correlations of differences of reactivities between the MAb and the species variants of insulin with the respective amino acid sequences of the latter have permitted the identification of two epitopes recognized by the MAb which encompass the regions in the A- and B-chains of insulin subject to frequent evolutionary amino acid substitutions. MAb 21 and H38 are directed to an epitope which includes residues B27-30 and A1 or A4 and can discriminate between human and pig insulins which differ only at B30. MAb 21 reacts with human (B30 thr) but not with pig (B30 ala) insulins, whereas MAb H38 exhibits a reciprocal specificity. Neither MAb 21 nor MAb H38 react with human or pig proinsulins respectively indicating that the presence of the C-peptide joining A1 to B30 masks the epitope. MAb 21 reacts with human insulin 125I-labeled at tyr A14 but not B26 suggesting that incorporation of the I atom at B26 also masks the epitope. MAb I10 is directed to an epitope which includes A8-10 and A4 or B3 with a specificity for the human A8-10 sequence. MAb I10 reacts with human proinsulin and human insulin 125I-labeled at either tyr A14 or B26.     

聚乙二醇在聚砜膜上的接枝与表征

对用紫外辐照法在聚砜膜表面接枝的聚乙二醇作了初步的研究。通过静态水接触角测定、X射线-光电子能谱分析以及原子力学显微镜等测试手段，对接枝前后聚砜膜表面的性能进行了测定，证明采用同步接枝法和二步接枝法在聚砜材料表面接上了聚乙二醇，表面亲水性大大提高，两种接枝方法的接枝覆盖率分别为77．3％和41．9％，表面形貌、相位图等参数较接枝前变化明显，说明用同步法在聚砜膜表面产生了分枝的聚乙二醇层，而二步法在聚砜膜表面产生了薄煎饼状的聚乙二醇层。这一研究为下一步拟在聚砜中空纤维膜表面接上聚乙二醇刷分子层打下了基础。     

Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis

Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year, placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract, in ragweed pollen-induced rhinoconjunctivitis. At the beginning of the study, subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year. There was random allocation of half to active treatment and half to placebo treatment. Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections (group 1), and the remaining 26 received six injections (group 2). Before the second season all subjects received 10 injections. Doses increased by half a log concentration each week unless there were adverse reactions. The mean total dose received by group 1 in year 1 was 385 micrograms of protein (28.9 micrograms AgE) and received by group 2 was 218 micrograms of protein (16.4 micrograms AgE). In year 2 the mean total dose was 1829 micrograms (137.2 micrograms AgE). Sixty-six percent of injections elicited no reaction or a mild local reaction; the remaining injections produced local redness and swelling more than 2 inches in diameter. Four percent of injections produced systemic symptoms. PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years, but increases in ragweed specific IgE antibody were significant only in group 1 in year 1. The magnitude of the IgG antibody changes was directly related to the total dose injected. At the beginning of the second year, PEG-modified ragweed-treated subjects still had elevated IgG antibody levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

mPEG表面修饰的PLGA嵌段共聚物的血液相容性评价

本实验室设计合成了三种不同LA／GA比例的mPEG修饰PLGA（PELGA，含15％mPEG），为了评价它们的血液相容性，我们以硅化玻璃试管为阴性对照，未硅化的试管为阳性对照，参照国际标准（ISO10993）和《中华人民共和国国家标准GB／T16886医疗器械生物学评价》方法进行了体外评价实验。试验包括溶血率实验，血小板黏附实验，动态凝血时间实验，凝血时间实验，血浆复钙时间实验和凝血酶原时间实验等综合评价指标。结果表明，合成材料具有优良的血液相容性，材料制成的纳米粒有望应用于静脉注射。     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.