亚临床肝性脑病患者的血清锌,铜含量的测定及临床意义

检测了３０例慢性活动性肝炎患者、３０例肝硬化患者、３０例亚临床肝性脑病患者血清中的铜、锌含量，并与正常对照组进行比较分析，探讨了微量元素铜、锌的血清含量改变及其影响因素，分析其临床意义。结果表明体内的铜锌含量与肝脏功能有密切的关系。在慢性活动性肝炎时，虽然肝脏功能有一定的损害，但由于肝脏的代偿能力强，铜，锌含量仍可保持在正常水平，而在肝硬化、亚临床肝性脑病时，铜锌明显降低，而铜锌含量的降低又导致机     

Synthesis of functionalized analogs of pyochelin, a siderophore of Pseudomonas aeruginosa and Burkholderia cepacia

Using an improved synthesis of pyochelin, a siderophore common to several pathogenic Pseudomonas species, three functionalized pyochelin analogs were efficiently synthesized starting from appropriate 2-hydroxybenzonitriles.     

桑蚕丝素蛋白的结构、形态及其化学改性

通过对桑蚕吐丝机构的描述,着重从高分子科学的角度介绍桑蚕丝和蚕丝素蛋白大分子的组成、形态及各种化学、物理性质,讨论了蚕丝素蛋白的纤维化机理,并简述了丝索蛋白纤维的化学接枝改性及其应用。     

A stereotypic,transplantable liver tissue-culture system

A method of coculturing adult rat hepatic parenchymal cells (PC) and stromal cells in a three-dimensional framework of nylon filtration screens or biodegradable polymer meshes was developed in our laboratory. Rat liver stroma, which includes vascular and bile duct endothelial cells, fat-storing cells, fibroblasts, and Kupffer cells, were isolated by gradient centrifugation afterin situ liver perfusion and expanded in monolayer culture prior to seeding onto nylon screens or bioresorbable polyglycolic acid (PGA) polymers oriented into a felt-like construct. A second inoculum of freshly isolated PC was applied after the stromal cells became established. Histological analyses revealed that PC proliferation occurred until all available space for expansion within the template was exhausted. These cells retained their rounded morphology, and after 4–5 wk 7–9 “layers” of PC filled the 140-μm deep template. Dioxin-inducible cytochrome P450 activity was detected for up to 58 d in culture, and albumin, fibrinogen, transferrin, and soluble fibronectin were detected in the medium by enzyme-linked immunosorbent assay (ELISA) for 48 d in vitro. Immunohistochemical analysis of sections through the cultures confirmed the presence of these proteins as well as cytokeratin at the cellular level; the extracellular matrix stained for both collagen type III and laminin. Long-term PC proliferation and function were enhanced by the presence of stromal cells as well as by a meshwork template whose geometry allows the interaction of PC with stroma and matrix on several different planes. To permit transplantation, co-cultures of hepatic PC and stromal cells were established on PGA felt constructs instead of nylon screens. After 24 d in vitro, these constructs were grafted into sites in the mesentery, omentum, and sub-cutaneous tissues of adult Long-Evans rats. The growth of hepatocytes after 30 din situ was evident by histological analysis; grafts of co-cultures regenerated a liver-like architecture consisting of sinusoids and putative biliary structures. In addition, PC at these extrahepatic graft sites were positive for albumin, transferrin, and fibrinogen synthesis by immunohistochemistry. Graft survival was enhanced when recipients were subjected to 40% hepatectomy. Hepatic PC:stromal cell cocultures may prove useful in the restoration of liver function either by direct transplantation using PGA or similar templates, or as extracorporeal devices, using nylon screens.     

Immunological detection of glycoproteins on blots based on labeling with digoxigenin

In the following, we describe the application of the DIG/antiDIG system for the (structural) analysis of glycoproteins on blots. Special emphasis is being placed on the variety of the different DIG applications in order to obtain structural information concerning the glycoprotein carbohydrate chains. Prominent among them is the use of lectins with well-known specificities for carbohydrate structures. This article first appeared in: Hounsell, E. F., ed. (1993),Methods in Molecular Biollogy, vol. 14: Glycoprotein Analysis in Biomedicine, Humana Press Inc., Totowa, NJ.     

Exhaled breath condensate: Determination of non-volatile compounds and their potential for clinical diagnosis and monitoring. A review

Exhaled breath condensate is a promising, non-invasive, diagnostic sample obtained by condensation of exhaled breath. Starting from a historical perspective of early attempts of breath testing towards the contemporary state-of-the-art breath analysis, this review article focuses mainly on the progress in determination of non-volatile compounds in exhaled breath condensate. The mechanisms by which the aerosols/droplets of non-volatile compounds are formed in the airways are discussed with methodological consequences for sampling. Dilution of respiratory droplets is a major problem for correct clinical interpretation of the measured data and there is an urgent need for standardization of EBC. This applies also for collection instrumentation and therefore various commercial and in-house built devices are described and compared with regard to their design, function and collection parameters. The analytical techniques and methods for determination of non-volatile compounds as potential markers of oxidative stress and lung inflammation are scrutinized with an emphasis on method suitability, sensitivity and appropriateness. The relevance of clinical findings for each group of possible non-volatile markers of selected pulmonary diseases and methodological recommendations with emphasis on interdisciplinary collaboration that is essential for future development into a fully validated clinical diagnostic tool are given.     

Determination of a novel antifibrotic small molecule GDC‐3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first‐in‐human clinical trial

A specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R² > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles.     

Pharmacokinetics,hepatic disposition,and heart tissue distribution of 14 compounds in rat after oral administration of Qi-Li-Qiang-Xin capsule via ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

In the present study, a specific and sensitive approach using ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated for the quantitative analysis of 14 constituents in rat plasma, liver, and heart. The method was fully validated and successfully applied to pharmacokinetic, hepatic disposition, and heart tissue distribution studies of 14 compounds after the oral administration of Qi-Li-Qiang-Xin capsule. Ginsenoside Rb1, alisol A, astragaloside IV, and periplocymarin were found to be highly exposed in rat plasma, while toxic components such as hypaconitine, mesaconitine, and periplocin had low circulation levels in vivo. Moreover, sinapine thiocyanate, neoline, formononetin, calycosin, and alisol A exhibited significant liver first-pass effects. Notably, high levels of alisol A, periplocymarin, benzoylmesaconine, and benzoylhypaconine were observed in the heart. Based on high exposure and appropriate pharmacokinetic features in the systemic plasma and heart, astragaloside IV, ginsenoside Rb1, periplocymarin, benzoylmesaconine, benzoylhypaconine, and alisol A can be considered as the main potentially effective components. Ultimately, the results provide relevant information for discovery of effective substances, as well as further anti-heart failure action mechanism investigations of Qi-Li-Qiang-Xin capsule.     

A novel imaging tool for hepatic portal system using phase contrast technique with hydrogen peroxide‐generated O2 gas

The objective of this study was to investigate the potential of hydrogen peroxide‐generated oxygen gas‐based phase contrast imaging (PCI) for visualizing mouse hepatic portal veins. The O₂ gas was made from the reaction between H₂O₂ and catalase. The gas production was imaged by PCI in real time. The H₂O₂ was injected into the enteric cavity of the lower sigmoid colon to produce O₂ in the submucosal venous plexus. The generated O₂ gas could be finally drained into hepatic portal veins. Absorption contrast imaging (ACI) and PCI of O₂‐filled portal veins were performed and compared. PCI offers high resolution and real‐time visualization of the O₂ gas production. Compared with O₂‐based ACI, O₂‐based PCI significantly enhanced the revealing of the portal vein in vivo. It is concluded that O₂‐based PCI is a novel and promising imaging modality for future studies of portal venous disorders in mice models.