Factor XI/ADAMTS13 complexes are quantitatively insignificant in human plasma

Reportedly, complexes between factor XI and ADAMTS13 are detected with a commercial ADAMTS13/FXI ELISA kit in plasma and are decreased in thrombotic thrombocytopenic purpura (TTP). Using this kit, control and TTP patient plasma contained varying amounts of signal (25-670% of a reference plasma) but no signal was observed for mixtures of recombinant enzymes, suggesting little interaction. ADAMTS13/FXI complexes were undetectable by immunoprecipitation or gel filtration chromatography in control plasma or mixtures of recombinant proteins. These results suggest that ADAMTS13/FXI complexes are insignificant in plasma and unlikely to affect the function of either protein during normal hemostasis or in TTP.     

Spontaneous pneumomediastinum in a patient with recent air travel

Spontaneous pneumomediastinum (SPM) is a fairly uncommon condition in which free air is present in the mediastinum, often in young patients without injury or serious underlying pulmonary disease. We present a case of SPM in a 36-year-old man with no pertinent medical history who presented with chest pain after a 3-h flight. To the best of our knowledge, this is the first known case in radiology literature of SPM caused by increased intra-alveolar pressure secondary to increased altitude.     

Two Cys residues essential for von Willebrand factor multimer assembly in the Golgi

Von Willebrand factor (VWF) dimerizes through C-terminal CK domains, and VWF dimers assemble into multimers in the Golgi by forming intersubunit disulfide bonds between D3 domains. This unusual oxidoreductase reaction requires the VWF propeptide (domains D1D2), which acts as an endogenous pH-dependent chaperone. The cysteines involved in multimer assembly were characterized by using a VWF construct that encodes the N-terminal D1D2D'D3 domains. Modification with thiol-specific reagents demonstrated that secreted D'D3 monomer contained reduced Cys, whereas D'D3 dimer and propeptide did not. Reduced Cys in the D'D3 monomer were alkylated with N-ethylmaleimide and analyzed by mass spectrometry. All 52 Cys within the D'D3 region were observed, and only Cys(1099) and Cys(1142) were modified by N-ethylmaleimide. When introduced into the D1D2D'D3 construct, the mutation C1099A or C1142A markedly impaired the formation of D'D3 dimers, and the double mutation prevented dimerization. In full-length VWF, the mutations C1099A and C1099A/C1142A prevented multimer assembly; the mutation C1142A allowed the formation of almost exclusively dimers, with few tetramers and no multimers larger than hexamers. Therefore, Cys(1099) and Cys(1142) are essential for the oxidoreductase mechanism of VWF multimerization. Cys(1142) is reported to form a Cys(1142)-Cys(1142) intersubunit bond, suggesting that Cys(1099) also participates in a Cys(1099)-Cys(1099) disulfide bond between D3 domains. This arrangement of intersubunit disulfide bonds implies that the dimeric N-terminal D'D3 domains of VWF subunits align in a parallel orientation within VWF multimers.     

炔诺酮肟(NETO)与炔诺酮(NET)在猴体内的药代动力学

利用HPLC分离和液闪测定放射性的方法,研究了恒河猴ⅳ和鼻饲NETO和NET的药代动力学。鼻饲后NETO和NET吸收迅速,24 h内均基本消除。鼻饲或ⅳNETO后,一部分迅速转变为NET,一部分以原药形式存在。两药的血药浓度—时间曲线符合po或ⅳ的二室开放模型。二原药的主要药代动力学参数无显著差异。NETO与NET的鼻饲绝对生物利用度分別为64.46±34.60与35.02±26.49%。     

Congenital orbital teratoma

Background: The occurrence of proptosis at birth unusual and may be associated with a variety of tumours and structural abnormalities. Congenital orbital teratoma a rare cause of congenital proptosis. Methods: A case report is presented of a female infant with gross right proptosis. Results: Computed tomography demonstrated a characteristic multicystic structure with no intracranial involvement. Histological examination found tissues derived from all three germ cell layers, consistent with a congenital orbital teratoma. The tumour was successfully removed preserving the globe and vision. Conclusions: This report is an example of how early surgical intervention may allow preservation of the globe and vision in some patients with congenital orbital teratoma.     

1,4-Azaindole,a Potential Drug Candidate for Treatment of Tuberculosis

New therapeutic strategies against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis are urgently required to combat the global tuberculosis (TB) threat. Toward this end, we previously reported the identification of 1,4-azaindoles, a promising class of compounds with potent antitubercular activity through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1). Further, this series was optimized to improve its physicochemical properties and pharmacokinetics in mice. Here, we describe the short-listing of a potential clinical candidate, compound 2, that has potent cellular activity, drug-like properties, efficacy in mouse and rat chronic TB infection models, and minimal in vitro safety risks. We also demonstrate that the compounds, including compound 2, have no antagonistic activity with other anti-TB drugs. Moreover, compound 2 shows synergy with PA824 and TMC207 in vitro, and the synergy effect is translated in vivo with TMC207. The series is predicted to have a low clearance in humans, and the predicted human dose for compound 2 is ≤1 g/day. Altogether, our data suggest that a 1,4-azaindole (compound 2) is a promising candidate for the development of a novel anti-TB drug.     

β-酪蛋白与婴幼儿生长和发育

<正>母乳是婴幼儿的首选营养源。世界卫生组织(WHO)建议婴儿出生后头6个月应完全以母乳喂养。此外,应坚持母乳辅以适当的固体食物喂养至少两年[1]。然而,并非所有婴儿均可得到母乳喂养,一些婴儿也无法获得捐赠母乳。在这种情况下需要用婴幼儿配方奶代替母乳。牛奶含有相对价廉的蛋白质与营养素且来源丰富,因此大多数婴幼儿配方奶均产自牛奶。但是,牛奶与母乳的蛋白质成分差异颇大。如,母乳主要含乳清蛋白,酪蛋白∶乳清蛋白约为40∶60(泌乳早期10∶90,泌乳后期50∶50),而牛奶的酪蛋白∶乳清蛋白则高达80∶20[2]。