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91.
Zhenling Liu Zhongping Xiao Sayaka Masuko Wenjing Zhao Eric Sterner Vinod Bansal Jawed Fareed Jonathan Dordick Fuming Zhang Robert J. Linhardt 《Analytical biochemistry》2011,(1):147
A quantitative analysis of a recalled contaminated lot of heparin sodium injection U.S. Pharmacopeia (USP) was undertaken in response to the controversy regarding the exact nature of the contaminant involved in the heparin (HP) crisis. A mass balance analysis of the formulated drug product was performed. After freeze-drying, a 1-ml vial for injection afforded 54.8 ± 0.3 mg of dry solids. The excipients, sodium chloride and residual benzyl alcohol, accounted for 11.4 ± 0.5 and 0.9 ± 0.5 mg, respectively. Active pharmaceutical ingredient (API) represented 41.5 ± 1.0 mg, corresponding to 75.7 wt% of dry mass. Exhaustive treatment of API with specific enzymes, heparin lyases, and/or chondroitin lyases was used to close mass balance. HP represented 30.5 ± 0.5 mg, corresponding to 73.5 wt% of the API. Dermatan sulfate (DS) impurity represented 1.7 ± 0.3 mg, corresponding to 4.1 wt% of API. Contaminant, representing 9.3 ± 0.1 mg corresponding to 22.4 wt% of API, was found in the contaminated formulated drug product. The recovery of contaminant was close to quantitative (95.6–100 wt%). A single contaminant was unambiguously identified as oversulfated chondroitin sulfate (OSCS). 相似文献
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Atsuyuki Tomizawa Itsuko Ishii Zhivko Zhelev Ichio Aoki Sayaka Shibata Mitsukazu Kitada Rumiana Bakalova 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
Gd-DTPA-enhanced magnetic resonance imaging (MRI) is a conventional method for non-invasive investigation of blood-brain-barrier (BBB) permeability in animal models. It allows the visualization of serious injury to the BBB. We developed a novel approach for detecting very small disruptions in BBB permeability induced by dietary cholesterol by using carbamoyl-PROXYL (CMP) as an MRI contrast probe.Methods
Mice were separated into two groups: normal diet (ND-mice) and high cholesterol diet (CD-mice). MRI-signal dynamics, plasma cholesterol, matrix metalloproteinase (MMP-9, MMP-2), and the white blood cell profile were analyzed. For the MRI analysis, two regions-of-interest (ROI) were selected: brain (ROI-1) and surrounding area (ROI-2).Results
In the ROI-2 of ND-mice, CMP- or Gd-enhanced MRI-signal followed typical kinetics with a half-life of signal decay (τ1/2) ~ 8 or ~ 15 min, respectively. In CD-mice, the MRI-signal increased continuously without decay.In the ROI-1 of ND- and CD-mice, MRI-signal enhancement was not detected by Gd-DTPA. In the ROI-1 of ND-mice, CMP-induced MRI-signal enhancement was negligible, while in CD-mice, it was significant (τ1/2 > 15 min).Hypercholesterolemia increased the plasma levels of MMP-9 and neutrophils.Conclusions
Hypercholesterolemia increases vascular permeability, which is mediated by MMP-9 and neutrophils.General significance
Even very small disruptions in brain vascular permeability could be detected by CMP-enhanced MRI but not by Gd-DTPA-enhanced MRI. 相似文献94.
Electrostatic interactions between lipids and proteins control many cellular events. We found that phospholipids, including phosphatidylinositol 3-phosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidylinositol 3,4,5-triphosphate, bound to the C-terminal coiled-coil region of par-3 at conserved, basic residues. We identified K1013 and K1014 as the phosphoinositide binding site, because the K1013E/K1014E mutation of rat par-3 abolished its lipid binding. Importantly, the K1013E/K1014E par-3 mutant exhibited significantly weaker localization at the cell-cell junctions than the wild-type par-3. Fluorescence recovery after photo-bleaching analyses confirmed the faster turnover of mutant par-3 at cell-cell junctions. The treatment of cells with an inhibitor of phosphatidylinositol 3-kinases partially increased the turnover of par-3. These data suggested that the putative phospholipid binding by par-3 is important for its localization at cell-cell junctions. 相似文献
95.
In this report, we propose a novel evaluation method of embryo activity, describing the real-time and noninvasive electrical
monitoring of embryo activity, caused by fertilization of the sea urchin, using a biologically-coupled field-effect transistor
(bio-FET) comprised of semiconductor-based biosensing devices. The detection principle of bio-FET is based on the potentiometric
detection of charge density change at the gate insulator, which includes changes of hydrogen ion concentration corresponding
to pH variation. The surface potential at the gate surface of the bio-FET increased after the introduction of sperms into
the ova, resulting in fertilization on the gate sensing area. The positive shift of surface potential indicates the increase
of positive charges of hydrogen ions generated by dissolved carbon dioxide in artificial sea water based on respiration activity
of the embryo. Moreover, the electrical signal of embryo activity is suppressed due to the inhibition of cytokinesis by introduction
of cytochalasin B. The platform based on the bio-FET is expected to be a real-time, label-free and noninvasive detection system,
not only in fundamental studies of embryo activity but also in the evaluation of embryo quality for in vitro fertilization. 相似文献
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The genome of the Friend murine leukemia virus (Fr‐MLV) contains a 5′ splice site (5′ss) located at 205 nt and a 3′ss located at 5489 nt. In our previous studies, it was shown that if the HindIII–BglII (879–1904 bp) fragment within gag is deleted from the proA8m1 vector, which carries the entire Fr‐MLV sequence, then cryptic splicing of env‐mRNA occurs. Here, attempts were made to identify the genomic segment(s) in this region that is/are essential to correct splicing. First, vectors with a serially truncated HindIII–BglII fragment were constructed. The vector, in which a 38 bp fragment (1612–1649 bp) is deleted or reversed in proA8m1, only produced splice variants. It was found that a 38 nt region within gag contains important elements that positively regulate splicing at the correct splice sites. Further analyses of a series of vectors carrying the 38 bp fragment and its flanking sequences showed that a region (1183–1611 nt) upstream of the 38 nt fragment also contains sequences that positively or negatively influence splicing at the correct splice sites. The SphI–NdeI (5140–5400 bp) fragment just upstream of the 3′ss was deleted from vectors that carried the 38 bp fragment and its flanking sequences, which yielded correctly spliced mRNA; interestingly, these deleted vectors showed cryptic splicing. These findings suggest that the 5140–5400 nt region located just upstream of the 3′ss is required for the splicing function of the 38 nt fragment and its flanking sequences. 相似文献
100.