纺缍形α-Fe2O3/聚苯乙烯复合高分子微球的制备、表征及等电性研究

以硝酸铁为原料，尿素为均匀沉淀剂，磷酸二氢钠为结晶助剂，用动态开放回流系统的均匀沉淀法制备了纺锤形α-Fe2O3粒子。并用XRD、TEM等进行了表征。当Fe(NO3)3、NaH2PO4、CO(NH2)2的浓度分别为0．20、0．0015、0．10mol／L，反应温度为117℃，陈化时间为13h时，制备的粒子轴比可达3．3，且分散性较好，粒径分布窄，陈化时间短，产率较高。对反应机理、结晶助剂NaH2PO4的作用等作了初步研究。并测量了不同pH值时粒子的Zeta电位值，找出了粒子的等电点，与理论估算值接近。     

Type II collagen in the early embryonic chick cornea and vitreous: Immunoradiochemical evidence

The relative proportion of collagen types I and II was examined in early chick corneas and vitrous bodies by radioimmunoprecipitation. Embryos (4–5 days of incubation) were labelled in ovo with ³H-proline. After an additional 1–2 days, corneas and vitreous bodies were removed and the collagen was extracted and treated by limited pepsinization. Then, the labelled collagens were reacted with affinity purified antibodies against collagen types I and II, and the immune complexes precipitated with protein A-containing Staphylococcus aureus. In some cases, the precipitated collagen was further analysed by SDS-polyacrylamide gel electrophoresis. The results for the vitreous showed that greater than 90% of the labelled material precipitated by the antibodies was in type II. In the corneal samples, on the other hand, both types of antibodies precipitated appreciable labelled collagen with somewhat less than half being type II (30–46%). These results are in agreement with our earlier biochemical observations on the relative content of type II collagen in these extracellular matrix-rich structures from embryonic avian eyes.     

In VivoInduced Malignant Hyperthermia in Pigs. III. Localization of Calcium in Skeletal Muscle Mitochondria by Means of Electronmicroscopy and Microprobe Analysis

Biceps femoris muscle biopsies of malignant hyperthermia susceptible (MH+) and non-susceptible (MH^-) Dutch Landrace pigs were studied ultrastructurally, and exchangeable calcium was demonstrated, using the antimonate precipitation technique in combination with electron probe x-ray microanalysis. Biopsies were taken before and during the administration of halothane-plus-succinylcholine and after dantrolene sodium treatment of the animals. MH+ muscle, taken before the MH triggering, showed a high proportion (about 35%) of cells with supercontraction. Both MH+ and MH^- muscle had broad but nearly identical ranges of cell diameter. Core-like structures were occasionally present in muscle from MH+ pigs. Muscle mitochondria from the MH+ pigs accumulated large amounts of calcium in their matrix compartment during the halothane-plus-succinylcholine induced MH crisis. This calcium loading in the course of time caused swelling and structural damage to the mitochondria. Skeletal muscle mitochondria from MH+ pigs did not show such a reaction pattern on challenge with halothane and succinylcholine. It is concluded that in MH+ pigs the challenge brings about an increase in myoplasmic free calcium, which is predominantly due to calcium influx from the extracellular fluid. This rise in cytosolic calcium causes the mitochondria to accumulate the cation in an energy-dependent way. These findings are discussed in relation to the diverging halothane and caffeine contraction responses of aerobic type I and anaerobic type II muscle fibres.     

Precipitation by Neomycin Compounds of Fatty Acid and Cholesterol from Mixed Micellar Solutions

Abstract The effect of the polybasic antibiotic neomycin on micellar solutions of labelled lipids and bile salts was studied both in vitro and in vivo. The addition of neomycin sulphate to simple micellar solutions of bile salts in vitro raised the pH of precipitation of the glycine conjugates and induced precipitation of the taurine conjugates of dihydroxy bile acids, but had no effect on the corresponding trihydroxy compounds. Addition of neomycin to mixed micellar solutions caused precipitation of most of the fatty acid, monglyceride and cholesterol, but a lesser proportion of bile salt. Precipitation of mixed micellar solutions by neomycin was conditional on the presence of fatty acid and progressively lessened above pH 6.5. Two basic derivatives, Compound R. I. T. 1,291 and N-methyl neomycin, also precipitated fatty acid, in contrast to the neutral compound X-acetyl neomycin. In vivo the uptake of labelled oleic acid and cholesterol from mixed micelles, one hour after intraduodenal administration to rats, was markedly decreased by the simultaneous administration of neomycin sulphate 10 to 50 mg. Similarly, in rats with cannulated intestinal lymphatics and bile ducts, the lymphatic transport of labelled fatty acid and cholesterol was also inhibited by neomycin, although this had no effect on the absorption and biliary re-excretion of labelled taurocholate and taurodeoxycholate. These results suggest that basic neomycin compounds precipitate mixed micellar solutions primarily by their ionic interaction with fatty acids, and thus can interfere with the absorption of both fat and cholesterol.     

Determination of Sex Hormone-binding Globulin in Human Semen by Selective Ammonium Sulphate Precipitation*

Summary: A simple method was developed to measure the SHBG capacities of human serum, semen and sperm cells. After suitable dilution, disintegration and addition of labelled dihydrotestosterone-1,2-³H or testosterone-1,2-³H, the SHBG was precipitated by the addition of saturated ammonium sulphate in a final concentration of 42.3%. The precipitate was centrifuged and the activity of the non-bound, labelled steroid was counted in an aliquot of the supernatant. Subtraction of this result from the total activity yielded the SHBG-bound steroid in μg/100 ml or nmol/1. Examination of 52 males gave normal values of x? = 13.91 nmol/1 (S.E.M. = 0,746) di-hydrotestosterone binding globulin (DHTBG) and x? = 11.67 nmol/1 (S.E.M. = 0.555) testosterone binding globulin (TBG) in serum, while the concentrations in the seminal plasma were x? = 10.89 nmol/1 (S.E.M. = 0,723) DHTBG and x? = 8.93 nmol/1 (S.E.M. = 0.625) TBG. x? = 5.57 ng/mg protein (S.E.M. = 0.516) DHTBG and x? = 4.91 ng/mg protein (S.E.M. = 0.440) TBG were found in the disintegrated sperm cells. Zusammenfassung: Bestimmung des sexualhormonbindenden Globulins (SHBG) in Humanejakulat durch selektive Ammoniumsulfat-Ausfällung Zur Messung der SHBG-Kapazität in Humanserum, -ejakulat und Spermatozoen wurde eine einfache Methode entwickelt. Nach entsprechender Verdünnung, Aufschlüsselung und Zugabe von markiertem Dihydrotestosteron-1,2-³H oder Test osteron-1, 2-³H wurde das SHBG durch Zugabe von gesättigter Ammoniumsulfatlösung in einer Endkonzentration von 42,3% ausgefällt. Der Niederschlag wurde zentrifugiert und die Aktivität des nichtgebundenen markierten Steroids in der separierten Flüssigkeit gemessen. Die Subtraktion dieses Wertes von der Totalaktivität ergab den SHBG-gebundenen Steroidwert in μg/100 ml oder umgerechnet in nmol/1. Die Untersuchung von 52 Männern ergaben Normalwerte von x? = 13,91 nmol/1 (S.E.M. = 0,746) des dihydrotestosteronbindenden Globulins (DHTBG) und x? = 11,67 nmol/1 (S.E.M. = 0,555) des testosteronbindenden Globulins (TBG) im Serum während die Konzentrationen im Ejakulatplasma x? = 10.89 nmol/1 (S.E.M. = 0,723) DHTBG und x? = 8,93 nmol/1 (S.E.M. = 0,625) TBG waren. x? = 5,57 ng/mg Protein (S.E.M. = 0,516) DHTBG und x? = 4,91 ng/mg Protein (S.E.M. = 0,440) TBG wurden in desintegrierten Spermatozoen gefunden.     

系统性红斑狼疮中内皮细胞相关自身抗原的鉴定

目的在内皮细胞中筛选与系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病相关的自身抗原。方法用免疫沉淀法以SLE病人血清中自身抗体捕获人脐带内皮细胞(human umbilical vein endothelial cell,HUVEC)相关抗原,并用双向电泳法分离免疫沉淀产物,然后用LC-MS-MS串联质谱鉴定与SLE病人血清反应的蛋白点。最后用Western blot法验证部分鉴定蛋白。结果相对于正常人血清对照,SLE病人血清捕获了多个内皮细胞相关蛋白,质谱鉴定结果显示:通过免疫沉淀与双向电泳结合的方法成功鉴定了包括GAPDH等已知SLE自身抗原在内的一系列蛋白,其中钙/钙调蛋白依赖性丝氨酸蛋白激酶(calcium/calmodulin-dependent serine protein kinase,CASK)为新发现SLE候选自身抗原。并以重组人CASK蛋白证实SLE病人血清中CASK抗体水平显著高于正常人对照。结论内皮细胞蛋白CASK可能作为一个新的SLE相关自身抗原。     

Preparation and in-vitro evaluation of indomethacin nanoparticles

BACKGROUND AND THE PURPOSE OF THE STUDY: During the last two decades one of the most important problems in drug formulations has been low aqueous solubility of new molecules. However, numerous techniques, such as milling, co-solvent solubilization and solid dispersion have been used conventionally for aqueous solubility enhancement and the rate of solubility. Recently, nanoparticle engineering processes have been developed and reported for pharmaceutical applications to increase the dissolution rate of low-soluble drugs which in turn may leads to substantial increases in bioavailability. In this study, a controlled precipitation method was used to produce indomethacin nano-solid suspension in a polymeric matrix (as a model), in order to increase the solubility and rate of the dissolution of poorly soluble model drug. METHODS: Nano-solid suspension of indomethacin in polyvinyl pyrrolidine (PVP) was prepared by controlled precipitation technique, characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and evaluated for in vitro solubility and dissolution rate. RESULTS AND MAJOR CONCLUSION: Absence of thermal and diffractional peaks in DSC and XRD studies indicated that indomethacin interacts with PVP in solid phase. The solubility of indomethacin in nano-solid suspension compared to crystalline form was increased to about four-fold. It was found that particle size distribution depend to the polymer MW and drug: polymer ratios. Spectroscopy methods and Transmission Electron Microscopy (TEM) images showed that indomethacin dispersed as amorphous nanosize particles in freeze dried powder. Enhanced solubility and dissolution rate of indomethacin compared to physical mixtures and crystalline form of indomethacin (polymorph I), demonstrated that it interacts with PVP via hydrogen bond and probably forming eutectic mixture.     

比索洛尔对老年永久性心房颤动并慢性心功能不全患者心肌能量代谢变化的影响

目的以原儿茶醛为指标优化丹参醇沉工艺。方法首先采用Plackett-Burman设计对影响丹参醇沉操作的因素进行筛选,所选取的8个相关因素为:丹参水提浓缩液密度、一次醇沉加醇速度、一次醇沉液乙醇终浓度、一次醇沉浓缩液密度、二次醇沉加醇速度、二次醇沉液乙醇终浓度、氢氧化钠溶液的浓度和二次醇沉液的pH值。在此基础上,采用响应面法在线性范围内对影响醇沉操作的关键因素(丹参水提浓缩液密度、一次醇沉浓缩液密度和pH值)作了进一步的研究与探讨。结果通过对二次项回归方程求解得知,上述自变量中丹参水提浓缩液密度为1.15 mg.mL-1、一次醇沉浓缩液密度为1.26 mg.mL-1和pH值为7.68时,原儿茶醛含量达到最佳值为0.512 mg.mL-1。结论优化工艺的原儿茶醛提取含量高,可用于丹参醇沉过程中原儿茶醛的含量控制。     

Tissue compatibility and pharmacokinetics of three potential subcutaneous injectables for low‐pH drug solutions

Objectives The aim of the study was to investigate the tissue tolerance and bioavailability of four formulations containing 5% ricobendazole solubilised at low pH, following subcutaneous injection in sheep. Formulations were: a water‐in‐oil emulsion, a microemulsion, a hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD, 20%) drug solution, and a low‐pH drug solution (reference). Methods In‐vitro cytotoxicity of the formulations was investigated in L929 fibroblasts using MTS viability and lactate dehydrogenase leakage assays. Each formulation and respective vehicle was injected into either side of the back of a sheep to investigate the tissue tolerance and pharmacokinetics. Key findings In‐vitro studies suggested that both the emulsion and the microemulsion are unlikely to give a burst release of the low‐pH drug solution in aqueous media. The microemulsion showed the greatest in‐vitro cytotoxic effect but no significant difference was observed between the other formulations. In sheep, the three new formulations and vehicles caused little or no injection‐site reactions compared with a marked response to the reference formulation. Bioavailabilities of HP‐β‐CD formulation, emulsion and microemulsion formulations, relative to the reference formulation, were 194, 155 and 115%, respectively. Conclusions The three new subcutaneous injectables showed promise for reducing irritation of low‐pH solubilised ricobendazole. HP‐β‐CD significantly enhanced the drug absorption. Controlling the burst release of the low‐pH drug solution may improve tissue tolerance and minimise post‐injection precipitation, and hence increase drug bioavailability. The in‐vitro cytotoxicity studies did not predict the in‐vivo irritation effects.