壳聚糖、磷脂酰胆碱对轻度认知功能障碍患者脑组织氢质子磁共振波谱成像的影响

目的观察壳聚糖、磷脂酰胆碱对轻度认知功能障碍(MCI)患者海马氢质子磁共振波谱成像(1H-MRSI)的影响。方法对15例MCI患者(MCI组)和15名正常老年人(正常对照组)进行海马1H-MRSI检查。给予MCI组患者壳聚糖、磷脂酰胆碱治疗2个月后对其进行复查,比较N-乙酰天门冬氨酸(NAA)/肌酸(Cr)、胆碱(Cho)/Cr、肌醇(mI)/Cr的比值。结果与正常对照组相比,MCI组服药前、后NAA/Cr比值显著降低,mI/Cr比值显著升高(均P<0.05),Cho/Cr的差异无统计学意义。MCI组治疗后的NAA/Cr比值较治疗前明显升高(P<0.05),mI/Cr比值明显降低(P<0.05),Cho/Cr比值治疗前后的差异无统计学意义。结论1H-MRSI显示,壳聚糖和磷脂酰胆碱能改善脑组织的代谢,可能对MCI有一定的治疗作用。     

Novel colloidal associations of soyasaponins and lipid components (DPPC,cholesterol) as potential adjuvants for vaccines

Soyasaponins from soybean (Glycine max) represent promising new potent adjuvants for vaccine research because of their immunostimulating properties and weak hemolytic activity. In the present study, saponin microstructures of soyasaponins (soyasaponin Bb, soyasaponin Ab) with lipid components (cholesterol, DPPC (dipalmitoylphosphatidylcholine)) were designed by the lipid film method. In interaction studies between soyasaponins (soyasaponin Ab/Bb) and Langmuir monolayers (model membranes), composed of cholesterol and DPPC, marked interactions between soyasaponins and a pure cholesterol monolayer were observed. No interaction was detected for soyasaponins with a pure DPPC monolayer. The intercalation of soyasaponins in a mixed DPPC/cholesterol (3:1, w/w) monolayer was only observed for the monodesmosidic soyasaponin Bb whereas the second sugar chain of the bidesmosidic soyasaponin Ab impaired the access to the monolayer. Transmission electron microscopy was used for visualizing particle formation of soyasaponins and lipid components. Pseudo-binary systems (soyasaponin Ab/Bb, cholesterol) formed colloidal associations built up from ring-like subunits in the nanometer size range. In pseudo-ternary systems (soyasaponin, cholesterol, DPPC) soyasaponin Bb attacked the liposomal membrane by forming colloidal associations. Colloidal associations in pseudo-ternary systems with soyasaponin Ab, cholesterol and a phospholipid were only observed in the presence of PE (phosphatidylethanolamine) instead of DPPC. In an MTT assay with a HaCaT cell line (keratinocyte cell line) the cell viability was neither affected by the soyasaponins nor by the corresponding formulations. Both the pure soyasaponin solution and the saponin formulations may be promising adjuvant systems for the intradermal vaccine application. Furthermore, interaction studies between the model antigen ovalbumin and colloidal associations of saponins and cholesterol using MST (Microscale Thermophoresis) gave first indications of an antigen binding to colloidal associations. Ex vivo T-cell proliferation in the presence of soyasaponin Ab was confirmed.     

Quantitative and ultrastructural studies on the uptake of drug loaded liposomes by mononuclear phagocytes infected with Leishmania donovani

This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony gluconate after i.v. administration to mice infected with Leishmania donovani. It was demonstrated that entrapment within liposomes greatly altered the kinetics of uptake of the drug. We were also able to show that liposomes composed of sphingomyelin, stearylamine and cholesterol were marginally better than any other preparation in delivering entrapped drug to liver and spleen. X-ray microanalytical studies on the uptake of liposomes by Kupffer cells infected with L. donovani have indicated that internalised liposomes probably fuse with parasitophorous vacuoles, transferring their contents into the immediate locality of the leishmanial parasites. It is proposed that this is the way in which liposome entrapped antileishmanial agents have an enhanced therapeutic effect over free drug therapy.     

Decreased Biosynthesis of Lung Surfactant Constituent Phosphatidylcholine Due to Inhibition of Choline Transporter by Gefitinib in Lung Alveolar Cells

Purpose We investigated whether gefitinib, an anticancer agent, inhibits phosphatidylcholine (PC) biosynthesis and choline uptake by alveolar epithelial type II cells. Materials and Methods Uptake of choline and PC biosynthesis were examined in vitro, using human alveolar epithelia-derived cell line A549 and rat alveolar type (AT) II cells as models. Results Gefitinib reduced the incorporation of [³H]choline into PC in A549 and rat ATII cells. The uptake of [³H]choline by A549 and rat ATII cells was concentration-dependent, and the Km values were 15.0 and 10–100 μM, respectively. The uptake of [³H]choline by A549 and rat ATII cells was weakly Na⁺-dependent, and inhibited by hemicholinium-3. RT-PCR revealed expression of choline transporter-like protein (CTL)1 and organic cation transporter (OCT)3 mRNAs in both cells. The choline uptake by A549 and rat ATII cells was strongly inhibited by gefitinib with the IC₅₀ value of 6.77 μM and 10.5 μM, respectively. Conclusions Our results demonstrate that gefitinib reduces PC biosynthesis via inhibition of cellular choline uptake by A549 and rat ATII cells, which is mainly mediated by CTL1, resulting in abnormality of lung surfactant that can be one of mechanisms of the interstitial lung disease associated with gefitinib.     

多烯磷脂酰胆碱联合阿德福韦酯对拉米夫定耐药乙型肝炎的疗效

目的探讨阿德福韦酯联用多烯磷脂酰胆碱对耐拉米夫定慢性乙型肝炎的疗效及其安全性。方法选取医院收治的拉米夫定耐药慢性乙型肝炎患者120例,随机分为治疗组与对照组,治疗组给予多烯磷脂酰胆碱联合阿德福韦酯,对照组单纯给予阿德福韦酯。对比2组患者治疗前后肝功能变化、HBV DNA及HBeAg阳性患者阴转率,并在治疗后对2组患者耐药基因的变异率及不良反应的发生情况进行对比。结果与治疗前比较,治疗组与对照组患者的肝功能指标ALT、TBil和AST均显著降低,ALB水平显著升高。与对照组比较,治疗组肝功能指标水平改善更显著;治疗组HBV DNA阴转率及HBeAg阴转率显著升高,耐药基因变异率显著降低(P<0.05);治疗组出现1例(1.67%)乏力,对照组出现2例(3.33%)肌酸酶升高。结论多烯磷脂酰胆碱联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎疗效显著,安全性高。     

Model linear and star‐shaped polyisoprenes with phosphatidylcholine analogous end‐groups. Synthesis and association behavior in cyclohexane

Semitelechelic (ω‐), telechelic (α,ω‐), as well as 3‐ and 12‐arm star polyisoprenes (PI), end‐functionalized with the same dimethylamino group, were synthesized by anionic polymerization high vacuum techniques, using 3‐dimethylaminopropyllithium as initiator and chlorosilanes as linking agents. The dimethylamino groups were transformed to phosphatidylcholine analogues through reaction with 2‐ethoxy‐2‐oxo‐1,3,2‐dioxaphospholane. The association behavior of the phosphoro‐zwitterionic PI (PZw‐PI) was studied in cyclohexane by low angle laser light scattering, viscometry, and dynamic light scattering. The linear PZw‐PIs present relatively low weight‐average degree of association (N_w: 2–6), as compared with the corresponding sulfo‐zwitterionic PI (N_w: 10–45). The N_w values decrease with increasing molecular weight of the PI. In the case of the star PZw‐PI, the multiple intermolecular associations lead to the formation of gels, which break down by addition of a small amount of 1‐heptanol. In very dilute solutions and for high arm molecular weight stars, intramolecular dominates over intermolecular association.

     

异甘草酸镁与多烯磷脂酰胆碱治疗脂肪肝的疗效

目的 对比异甘草酸镁与多烯磷脂酰胆碱治疗脂肪肝患者的临床疗效.方法 依照数字分表法将本院2018年12月—2021年4月纳入的60例脂肪肝患者分为两组,每组患者30例,其中实行多烯磷脂酰胆碱治疗的为参照组,实行异甘草酸镁治疗的为观察组,比较治疗效果.结果 对比参照组,观察组血脂水平显著低,差异有统计学意义(P<0.05...