Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68

Solid dispersions using Pluronic F-68 as a carrier were studied for improving the dissolution and bioavailability of ABT-963, a poorly water-soluble compound. The solid dispersions were prepared either by evaporation of the ethanol solutions containing ABT-963 and Pluronic, or by cooling the hot melt of the drug in the carrier. The dispersions were characterized using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy, elemental mapping, and by constructing the melting point phase diagram. In vitro dissolution and in vivo oral bioavailability in fasted dogs were compared for the solid dispersion and a conventional IR capsule formulation. Results showed that, at a composition of approximately 7.5%, ABT-963 formed a eutectic mixture with Pluronic F-68. Both the drug and the polymer were crystalline in the solid dispersion with a wide range of composition of each component. The solid dispersion substantially increased the in vitro dissolution rate of ABT-963. Dosing of the dispersion to fasted dogs resulted in a significant increase of oral bioavailability compared with the conventional IR capsule formulation. These results show that solid dispersion is a promising approach for developing ABT-963 drug products.     

Increased incorporation of L-(U-14C)serine into phosphatidylserine in polymorphonuclear cells from cluster headache patients

It has recently been demonstrated by our group that polymorphonuclear cells (PMNs) from cluster headache patients incorporate more arachidonic acid (AA) into phosphatidylserine (PS) than PMNs from controls. In the present report, the incorporation of L-(U-14C)serine into PS in PMNs from 14 healthy volunteers and 12 cluster headache patients was studied. PMNs from controls incorporated 1194 +/- 578 (mean +/- SD) cpm of L-(U-14C)serine into PS, 268 +/- 292 cpm into phosphatidylethanolamine, and 57 +/- 71 cpm into sphingomyeline. The corresponding figures in cluster headache patients were 2365 +/- 841 cpm, 291 +/- 207 cpm, and 88 +/- 66 cpm, respectively. Incorporation of L-(U-14C)serine into PS was significantly increased (p less than 0.0004) in PMNs from cluster headache patients, whereas no significant difference was seen in other lipids. The results confirm that patients with cluster headache have an increased incorporation of precursors into PS in isolated PMNs, and they indicate that this is due to an increased de novo synthesis of PS.     

Cluster headache: Further observations on the dissociation of pain and autonomic findings

A 51-year-old male cluster headache patient had during five bouts in the course of 11 years always had the headache attacks on the left side. Autonomic abnormalities were, however, present on the right side. Pupillometrically, there was thus a Horner-like syndrome on the right (non-symptomatic) side, with miosis and a relatively more marked dilatation of that eye subsequent to topical application of a directly working sympathomimetic agent (phenylephrine) than after an indirectly working one (hydroxyamphetamine), whereas this was not the case on the symptomatic side. The findings on evaporimetry were not as clear-cut as the pupillometric findings; however, even facial sweating was consistent with a pathologic condition on the right (non-symptomatic) side. A primary dichotomy of pain and autonomic signs (that is, not due to change of side of pain localization) thus seems to be present in this case.     

5-氨基-2,4,6-三碘异酞酸的合成

目的：合成非离子含碘造影剂的中间体5－氨基－2，4，6－三碘异酞酸。方法：以间苯二酸为原料，经硝化、还原与碘化，合成5－氨基－2，4，6－三磷异酞酸。结果：每步均经改进，总收率达50.2%，所得产品熔点、IR、^1HNMR、^13CNMR光谱数据，与文献报道一致。结论：本工艺路线方法简单，原料易得，易工业化生产。     

Cluster headache: increased incorporation of (1-14C)arachidonic acid into phosphatidylserine in polymorphonuclear cells

Vasoactive metabolites deriving from arachidonic acid (AA) have been considered as putative mediators in the pathogenesis of various types of headache. In the present study we therefore compare the ability to synthesize AA containing precursor phospholipids in polymorphonuclear cells (PMNs) from healthy controls and cluster headache patients. 3.7% ± 1.4 (mean ± SD) of the (1-¹⁴C)AA incorporated into total PMN glycerophospholipids (GPLs) was recovered in the phosphatidylserine (PS) in a group of cluster headache patients ( n = 12). This was almost twice the value of 1.9% ± 0.8% found in a corresponding group of 24 healthy controls ( p < 0.001). A significant decrease in the incorporation of (1-¹⁴C)AA into phosphatidylcholine (PC) ( p < 0.01) and an increase in the incorporation of (1-¹⁴C)AA into phosphatidyletanolamine (PE) ( p < 0.05) were also found in cluster headache patients when compared to the control group. The increased incorporation of (1-¹⁴C)AA into PS in PMNs from this group of patients is interesting because PS plays an important role in the activation of protein kinase C, an enzyme involved in transmembrane signalling. The clinical implications of the present findings in cluster headache, if any, cannot yet be defined.     

前成骨细胞MC3T3-E1在梯度TiO2涂层修饰钛上的增殖与分化

目的:为改善纯钛的生物活性,对其表面进行梯度氧化钛生物活性涂层修饰,观察前成骨细胞MC3T3-E1在梯度氧化钛涂层修饰的钛上的黏附、增殖、形态和分化,评价该梯度涂层的生物活性。方法:实验于2006-03/12在清华大学生物膜与膜生物工程国家重点实验室完成。①梯度涂层的制备:先用阳极氧化的方法在纯钛上制备一层致密的氧化钛膜,而后在该致密膜上用微弧氧化法生成一层多孔的氧化钛膜。②细胞接种:将前成骨细胞MC3T3-E1接种到梯度涂层修饰的钛试件上(梯度改性试件),未修饰的钛和只有一层氧化钛修饰的钛试件也同样接种细胞作为参照。③观察指标:接种3h和6h后用MTT的方法检测细胞的黏附情况;培养3d后用扫描电镜观察细胞的生长形态;分别在培养7,14和21d后用MTT的方法分析MC3T3-E1细胞的增殖情况;将接种细胞的3种试件放于诱导培养基中,诱导培养28d后通过检测碱性磷酸酶的活性来分析细胞向成骨细胞的分化情况。结果:①接种3h后,在未修饰的钛和氧化改性试件上黏附的细胞数相近,比在梯度改性试件上的黏附细胞数要少;6h后在梯度改性试件上的细胞数的增加更显著,是未修饰的钛上细胞数的1.5倍。②培养3d后扫描电镜观察到细胞在所有材料上都能够正常生长,细胞在3种材料上的形态比较相似,都表现出正常MC3T3-E1细胞的形态。③MC3T3-E1细胞在所有试件上都随时间而有所增殖。在梯度改性试件上的细胞数最高,未修饰的钛上的细胞数最少,在7d的差别不是很明显,而第21天时梯度改性试件上的细胞数是纯钛上细胞数的4倍。④在诱导培养基中培养28d后,在梯度改性试件上培养的MC3T3-E1细胞的碱性磷酸酶活性是最高的,是纯钛试件的2倍。结论:MC3T3-E1细胞在梯度改性试件上的黏附、增殖和分化都是3种试件中最好的,表明梯度氧化钛涂层修饰的钛比纯钛或只有一层氧化钛修饰的钛都具有更好的生物活性。     

脑卒中后偏瘫手运动功能的恢复：纵向fMRI对照

目的:观察脑卒中后偏瘫手运动功能恢复后纵向fMRI表现。方法:于2003-12/2006-02选择中山大学第二附属医院神经内科收治的脑卒中患者11例,为脑卒中组。经CT或MRI证实脑梗死、出血,病灶可以累及运动皮质、内囊、基底节或脑干。发病时患侧手握力至少减低到4-级或以下。康复期(到行fMRI时)握力恢复到4 级以上,所用康复方法不限。行fMRI检查时间分别在发病后2个月和6个月。患者均知情同意。同期选择健康体检者15例为正常对照组,均为右利手,其中7例完成双侧手运动fMRI,另8例仅完成右侧手运动fMRI。观察指标:①非量化指标:观察双侧主要感觉运动区(Primary sensorimotor cortex,SM1)的激活位置、形态、范围和分布,观察运动前区(Premotor cortex,PM)、补充运动区(Supplementary motor area,SMA)、角回运动区(Cingulate motor areas,CMA)和非运动区的激活出现率。②量化指标:测量SM1的激活体积:用感兴趣区技术测量每一层SM1区激活的面积,相加后乘以层厚。侧方指数按公式计算:侧方指数=(对侧SM1激活体积-同侧SM1激活体积)/(对侧SM1激活体积 同侧SM1激活体积)。结果:①正常对照组受试者手运动SM1区fMRI表现:激活区在中央前后回区,可在侧脑室顶以上2￣6个层面观察到。激活区的形态呈斑片或不规则状,不同个体或左右手之间不完全相同。右、左手运动的对侧SM1激活体积、同侧SM1激活体积和侧方指数相近,差异无显著性意义(P>0.05)。②正常对照组受试者手运动非主要运动区和非运动区fMRI表现:非主要感觉运动区及非运动区的激活体积明显比SM1区小,以PM激活的出现率最高,CMA激活出现率最低,其他非运动区,除颞叶、枕叶外,出现率都比较低或无出现激活。③脑卒中后偏瘫手运动SM1区fMRI表现:在脑卒中后的2个月和6个月,无论哪侧患肢运动,在双侧SM1区均表现为斑片或不规则的激活影像,与正常对照组的激活区相似。脑卒中患者梗死后2个月与6个月右、左侧患手运动对侧SM1激活体积相近;梗死后2个月右、左侧患手运动同侧SM1激活体积大于梗死后6个月;梗死后2个月右、左侧患手运动侧方指数小于梗死后6个月;差异均无显著性意义(P>0.05)。④脑卒中患者梗死后2个月:右、左侧患手运动时,对侧SM1激活体积与正常对照组接近,差异无显著性意义(P>0.05);同侧SM1激活体积明显大于正常对照组[分别为(997±704),(195±152)mm3;(1661±962),(352±399)mm3],差异有显著性意义(t=4.312,3.240,P<0.05)。右、左手侧方指数明显小于正常对照组(分别为0.258±0.679,0.853±0.104;0.042±0.553,0.726±0.299),差异有显著性意义(t=-3.405,-3.285,P<0.05)。⑤脑卒中患者梗死后6个月:右、左侧患手运动时,对侧SM1激活体积与正常对照组接近,差异无显著性意义(P>0.05);右侧患手同侧SM1激活体积明显大于正常对照组[分别为(717±915),(195±152)mm3],差异有显著性意义(t=2.201,P<0.05);左侧患手同侧SM1激活体积大于正常对照组,差异无显著性意义(P>0.05);右、左手侧方指数小于正常对照组,差异无显著性意义(P>0.05)。⑥脑卒中后偏瘫手运动非主要运动区和非运动区fMRI表现:非主要运动各区和非运动区的激活体积比SM1区小,非主要运动区梗死后2个月时双侧PM、CMA激活区出现率均高于梗死后6个月;梗死后2个月时右侧SMA激活区出现率高于梗死后6个月,左侧SMA激活区出现率低于梗死后6个月。非运动区左颞叶区、左额前区、左顶后区激活出现率稍高,丘脑、基底节出现率稍低,梗死后2个月与6个月比较总体差别不大。结论:脑卒中后康复者,其对侧SM1激活体积在早期(梗死后2个月)已趋向稳定,同侧SM1区早期仍有明显代偿现象,晚期(梗死后6个月)趋向正常。     

骨科手术中联合应用电动气压止血带和驱血带

0引言止血带、驱血带是四肢手术中最常见的辅助工具,使用后可使手术视野清晰,手术操作方便,缩短手术时间,减少患者痛苦[1].     

砷与肝损伤

砷是一种环境有毒物质.近年来流行病学研究表明长期、过量摄入砷可导致暴露者出现不同程度的肝损害,严重危害人类健康.砷暴露致肝脏损害的临床表现以乏力、纳差、恶心、腹痛、腹胀、肝肿大等为主,并伴有门脉高压,血清转氨酶升高或不升高等,肝脏活检组织病理可见广泛肝细胞及细胞器的肿胀、变性为主,晚期则以存在不同程度肝细胞坏死及纤维增生为著.砷致肝病的研究越来越引起人们的重视.     

Sex- and age-dependent association of <Emphasis Type="Italic">SLC11A1</Emphasis>polymorphisms with tuberculosis in Chinese: a case control study

Background  

Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB.