Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat hepatocytes is mediated by Oatp1 and Oatp2

The uptake of the sulfated bile acid sulfolithocholyltaurine (SLCT) was investigated in isolated rat hepatocytes and in HeLa cells transfected with complementary DNAs (cDNAs) of organic anion transporting polypeptides (Oatps) 1 and 2 cloned from rat liver. In hepatocytes, transport of SLCT was greatly reduced by bromosulfophthalein (BSP), estrone sulfate, the precursor bile acids cholyltaurine and lithocholyltaurine, and 4,4'-diisothiocyanostilbene-2-2'-disulfonic acid (DIDS). However, SLCT transport was insensitive to 4-methylumbelliferyl sulfate, harmol sulfate, digoxin, fexofenadine, and lack of sodium ion. Because the estimation of kinetic constants was enhanced with use of inhibitors, BSP (1-50 micromol/L) was added to isolated rat hepatocytes to assess the various transport components for SLCT uptake. The resulting data showed a nonsaturable pathway and at least 2 pathways of different Michaelis-Menten constants (K(m)) (70 and 6 micromol/L) and similar maximum velocities (V(max)) (1.73 and 1.2 nmol/min/mg protein) and inhibition constants of 0.63 and 10.3 micromol/L for BSP. In expression systems, SLCT was taken up by Oatp1 and Oatp2 expressed in HeLa cells with similar K(m) values (12.6 +/- 6.2 and 14.6 +/- 1.9 micromol/L). These K(m) values were comparable to that observed for the high-affinity pathway in rat hepatocytes. In conclusion, the results suggest that transport of SLCT into rat liver is mediated in part by Oatp1 and Oatp2, high-affinity pathways, a lower-affinity pathway of unknown origin, and a nonsaturable pathway that is compatible with a transport system of high K(m) and/or passive diffusion.     

替米沙坦改善代谢综合征患者血管内皮功能

目的观察替米沙坦对代谢综合征患者血管内皮功能的影响。方法 76例代谢综合征患者随机分为常规组和替米沙坦组,每组38例,同时选择健康体检者38例作为对照组。替米沙坦组在常规用药的基础上加服替米沙坦80 mg/d,治疗3个月。检测三组患者治疗前后血糖、血脂代谢指标、血浆一氧化氮含量及炎症因子肿瘤坏死因子α、白细胞介素6和C反应蛋白水平,观察血压及血管内皮舒张功能变化。结果治疗后常规组和替米沙坦组的血压、空腹血糖均明显下降(P<0.01),但两组间的血压、空腹血糖相比差异无统计学意义(P>0.05)。治疗后替米沙坦组的肱动脉血流介导的舒张内径(FMD)(P<0.05)、一氧化氮含量明显升高(P<0.01),肿瘤坏死因子α、白细胞介素6和C反应蛋白水平降低(P<0.05),且与常规组相比差异有统计学意义(P<0.05);而常规组FMD、一氧化氮含量及炎症因子水平与治疗前比无明显变化(P>0.05)。结论替米沙坦可降低代谢综合征患者血浆炎症因子水平,抑制炎症反应,升高一氧化氮含量,改善血管内皮功能。     

A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers

Please cite this paper as: MacIntyre et al. (2011) A cluster randomized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00198.x. Background We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). Methods A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza‐like illness (ILI), laboratory‐confirmed respiratory virus infection and influenza. A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared. Findings The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory‐confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention‐to‐treat analysis, when P values were adjusted for clustering, non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high‐risk procedures were not. Interpretation Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 ( http://www.anzctr.org.au ).     

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period.     

结核分枝杆菌环介导恒温扩增（LAMP）快速检测方法的评价

目的 对国内建立的结核分枝杆菌DNA环介导恒温扩增（loop-mediated isothermal amplification, LAMP）快速检测方法进行了介绍和评价。 方法 实验菌株来源于北京结核病胸部肿瘤研究所。以结核分枝杆菌作为研究对象,设计了4 条LAMP 引物特异地识别结核分枝杆菌中 gyr B 基因的6个特殊区域。所有的菌株样本提取DNA作为模板,加入LAMP反应管后,65 ℃恒温反应60 min即可。其结果可以通过肉眼观察到的颜色变化来判断。 结果 实验共验证了79株临床和标准菌株。对于菌株的培养物,LAMP实验的灵敏度为100%,特异度为92%。 结论 结核分枝杆菌LAMP快速检测方法是一种快速、可靠的结核分枝杆菌诊断方法。     

Combination of sildenafil and simvastatin ameliorates monocrotaline-induced pulmonary hypertension in rats

Sildenafil, a phosphodiesterase-5 inhibitor, and simvastatin, a cholesterol lowering drug, both have therapeutic effects on PAH; however, the combination of these drugs has not been tested in the treatment of PAH. The purpose of this study was to determine whether the combination of sildenafil and simvastatin is superior to each drug alone in the prevention of MCT-induced PAH. Phosphorylated Smad levels were decreased in lung tissue in MCT-injected rats, whereas ERK protein levels were increased. This indicates a possible role for an increase in mitogenic ERK activity in addition to decreased proapoptotic Smad signaling in the MCT model of PAH. Combination sildenafil and simvastatin treatment prevented the MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH), exerted an anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC). Our results indicate that combination therapy with sildenafil and simvastatin attenuated the development of pulmonary hypertension more than either treatment alone.     

肾移植后血管并发症介入治疗8例

背景:肾移植后血管并发症采用介入治疗已成为一种安全有效的治疗方法。目的:探讨肾移植后血管并发症介入治疗的经验及价值评估。方法:回顾性分析8例肾移植后血管并发症患者介入治疗的临床资料。结果与结论:8例移植后5例肾移植肾动脉狭窄,2例假性动脉瘤,1例肾静脉血栓,均经彩色多普勒血流显像作出初步诊断,其中5例进一步行磁共振血管成像明确诊断。5例移植肾动脉狭窄行球囊扩张,分别随访6,8,20,36,40个月,1例出现再狭窄,随访血肌酐维持在130~160μmol/L之间,其余4例移植肾狭窄无复发,随访血肌酐均正常。2例假性动脉瘤患者经动脉鞘放入支架释放系统释放带膜支架后动脉瘤消失,目前常规血液透析治疗。1例肾静脉血栓形成患者,尿激酶介入溶栓治疗后血栓消失,患者发生移植肾功能延迟恢复,35d后血肌酐降至210μmol/L,此后患者血肌酐维持在200～250μmol/L。8例介入治疗临床效果说明肾移植后血管并发症治疗可选用介入治疗方法。     

鱼卵提取物微量刺激法诱导鼠脾细胞表达干细胞标志抗原

背景：小鼠和人的体细胞能被一些特殊的因子诱导,逆转为类似胚胎细胞的状态,即诱导性多能干细胞。目的：进一步提高鱼卵提取物诱导体细胞逆向分化为多能干细胞的效率。方法：以鱼卵提取物诱导BALB/C小鼠脾细胞分化为多能干细胞,分别以普通诱导法（鱼卵提取物质量浓度分别为0,0.1,0.2,0.4,0.8,1.2g/L）与微量刺激法诱导（鱼卵提取物质量浓度分别为0,0.05,0.1,0.2,0.4g/L）。结果与结论：与普通诱导法比较,微量刺激法诱导的脾细胞表达更多的干细胞标志抗原OCT-3/4,Nanog,SSEA-1。证明微量刺激法可进一步提高体细胞逆向分化为多能干细胞的效率。     

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway.