Tranexamic acid through intravenous,intramuscular and oral routes: an individual participant data meta‐analysis of pharmacokinetic studies in healthy volunteers

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.     

谷氨酸诱导体外培养的鸡胚脊髓神经细胞释放NO

用鸡胚脊髓神经细胞的原代培养,测定细胞中亚硝酸盐的含量,研究了谷氨酸(Glu)对原代培养神经细胞中NO的影响。结果表明,谷氨酸作用于原代培养的鸡胚脊髓神经细胞,在诱导神经细胞释放乳酸脱氢酶(LDH)的同时,还可诱导细胞释放一氧化氮(NO)。如先用NO合成酶抑制剂L-NOARG作用细胞,再加入Glu,则发现L-NOARG能降低Glu导致的培养液中LDH活性升高。提示NO可能参与介导Glu的神经毒性作用。     

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

吡酮酸类抗菌药物的研究Ⅷ.1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其类似物的合成和构效关系

为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。     

The Effect of Anti-Tuftsin Antibody on the Phagocytosis of Bacteria by Human Neutrophils

Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide which stimulates most known functions of the polymorphonuclear and mononuclear phagocytic cell lines. Although tuftsin is a well characterized bioactive peptide, the exact physiological role tuftsin plays remains unclear. Specific mouse anti-tuftsin antiserum generated in our laboratory, is now available for phagocytosis inhibition studies. Monolayers of human neutrophils were prepared on glass coverslips from a few drops of finger prick blood obtained from a single healthy donor. The monolayers were treated with and without mouse anti-tuftsin antiserum at dilutions of 1:1000 or 1:2000. Exogenous tuftsin (1 μg/ml) was also added with and without antibody. Treated and untreated neutrophils were subsequently incubated with unopsonized Staphylococcus aureus. The proportion of cells accomplishing phagocytosis (phagocytic index) and the number of bacteria engulfed per cell (avidity index) were recorded. The results showed that exogenous tuftsin increased phagocytosis while the addition of mouse anti-tuftsin antiserum at a 1:1000 dilution inhibited phagocytosis both with and without exogenous tuftsin. This effect was diminished by the antiserum at the 1:2000 dilution. This study reaffirms that tuftsin plays an important physiological role in phagocytosis.     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

Japanese encephalitis after a two-week holiday in Bali

Japanese encephalitis is described in a 10-year-old girl after a short holiday in Bali. Four days after returning to Australia the patient presented with a high fever, stupor and rapidly-developing focal neurological signs. Recovery occurred gradually over a period of three months and she has returned to school. Japanese encephalitis viral infection was confirmed by a marked rise in specific haemagglutination-inhibition antibodies and the presence of immunoglobulin M antibodies to the flavivirus group. It is important to be aware of the possibility of arboviral infection in patients with encephalitis. In view of the recent outbreaks of Japanese encephalitis in Asia, travellers to the region should be warned to protect themselves from mosquito-bites.     

CongenitaI Polycystic Disease of the Brain: Report of an Unusual Case

Multiple congenital supratentorial intracerebral cysts occurred in a newborn infant. The cysts, of varying size, content and lining, occupied the cerebral hemispheres. They formed a mosaic pattern on CT scan and left no trace of a recognisable ventricular system. Multiple surgical procedures were performed during the first year of life, and at one year the child was very well and asymptomatic, with two functioning shunts.