基于斑马鱼的香青兰总黄酮整体发育急性毒性评价研究

目的 利用模式生物斑马鱼研究香青兰总黄酮（TFDM）整体发育急性毒性。方法 采用发育至48 h的斑马鱼暴露于5、10、20、40、42、44、46、48、50、100 μg·mL^-1的TFDM,分别于暴露后24、48 h（24、48 hpe）,计算死亡率、半数死亡浓度（LC₅₀）值;测量每组斑马鱼幼鱼的体长,进行形态学观察并评分;显微镜下观察斑马鱼心脏形态并拍照,记录心率,使用Image-Pro Plus 5.1测量斑马鱼静脉窦-动脉球（SV-BA）距离;显微镜下观察各组斑马鱼是否有体侧水肿来判断TFDM对肾脏的影响并拍照;应用肝脏标记绿色荧光的转基因斑马鱼Tg （L-FABP∶EGFP）,通过检测肝脏荧光强度和面积,观察TFDM对肝脏毒性的影响。结果 TFDM的24 hpe LC₅₀为50 μg·mL^-1,48 hpe LC₅₀为48 μg·mL^-1,100 μg·mL^-1 TFDM组斑马鱼幼鱼全部死亡。与空白对照组比较,20 μg·mL^-1以下的TFDM对斑马鱼的形态和心、肝、肾各脏器无影响;20 μg·mL^-1浓度的TFDM处理斑马鱼48 h导致个别斑马鱼鱼鳔体积减小或缺失,对其他脏器无显著影响;40 μg·mL^-1的TFDM导致斑马鱼出现轻微的心包水肿,处理48 h以后斑马鱼体长显著减小（P＜0.01）,形态评分显著下降（P＜0.01）,斑马鱼的肝脏形态出现轻微变化,但肝脏荧光强度和肝脏荧光面积无显著性变化,对肾脏无影响;暴露在50 μg·mL^-1的TFDM中24 h,斑马鱼出现心包水肿,心率显著下降（P＜0.05）,肝脏荧光强度和面积显著减小（P＜0.05）,肾脏无明显变化。结论 TFDM对斑马鱼的毒性较小,低浓度（≤10 μg·mL^-1）的TFDM对斑马鱼无毒性;中浓度（20 μg·mL^-1）下TFDM对斑马鱼的毒性微弱,仅导致部分斑马鱼鱼鳔体积减小或缺失,对其他各脏器无毒性;高浓度（≥40 μg·mL^-1及以上）下有轻微的心脏毒性和肝脏毒性,在临床应用中有必要合理控制用量。     

Localization,mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice

Background

Nanobodies are single‐domain antigen binding fragments derived from functional heavy‐chain antibodies elicited in Camelidae. They are powerful probes for radioimmunoimaging, but their renal uptake is relatively high. In this study we have evaluated the role of megalin on the renal uptake of anti‐EGFR ^99mTc‐7C12 nanobody and the potency of gelofusine and/or lysine to reduce renal uptake of ^99mTc‐7C12.

Methods

First we compared the renal uptake of ^99mTc‐7C12 in megalin‐deficient and megalin‐wild‐type mice using pinhole SPECT/microCT and ex vivo analysis. The effect of gelofusine and lysine administration on renal accumulation of ^99mTc‐7C12 was analyzed in CD‐1 mice divided into lysine preload at 30 min before tracer injection (LysPreload), LysPreload + gelofusine coadministration (LysPreload + GeloCoad), lysine coadministration (LysCoad), gelofusine coadministration (GeloCoad) and LysCoad + GeloCoad. The combined effect of gelofusine and lysine on tumor uptake was tested in mice xenografts.

Results

Renal uptake of ^99mTc‐7C12 was 44.22 ± 3.46% lower in megalin‐deficient compared with megalin‐wild‐type mice. In CD‐1 mice, lysine preload had no effect on the renal retention whereas coinjection of lysine or gelofusine with the tracer resulted in 25.12 ± 2.99 and 36.22 ± 3.07% reduction, respectively. The combined effect of gelofusine and lysine was the most effective, namely a reduction of renal retention of 45.24 ± 2.09%. Gelofusine and lysine coadministration improved tumor uptake.

Conclusion

Megalin contributes to the renal accumulation of ^99mTc‐7C12. Gelofusine and lysine coinjection with the tracer reduces the renal uptake while tumor uptake is improved. Although this methodology allows for optimization of imaging protocol using nanobodies, further improvements are needed before using these molecules for radionuclide therapy. Copyright © 2010 John Wiley & Sons, Ltd.     

异位肾的外科手术治疗:附35例报告

目的探讨异位肾的外科手术治疗策略,并评价其临床疗效。方法回顾性分析我院2000年1月～2009年10月间35例异位肾患者的临床资料,术前经B超、静脉尿路造影、膀胱镜、CT、MRU和放射性核素等检查明确诊断。其中异位肾合并同侧输尿管异位开口26例(重复肾重复输尿管畸形3例),异位肾合并中度或重度积水9例(异位肾结石3例),大部分患者均有不同程度的肾脏发育不良(24/35)。所有患者均采用手术治疗,行异位肾切除术25例,异位肾输尿管膀胱再植术7例,异位肾肾盂切开取石术3例。结果术后随访7～29月,35例患者均取得满意疗效。结论根据异位肾合并的畸形及并发症采取相应的外科手术治疗策略,可以获得良好的临床效果。     

自拟益肾汤治疗早期糖尿病肾病的效果观察

目的：观察自拟益肾汤治疗早期糖尿病肾病的临床效果。方法：选取我院2007年1月～2009年12月120例早期糖尿病肾病患者,分为观察组（方剂治疗组）和对照组（常规治疗组）各60例,比较两组6周后临床症状及肾功能改善情况。结果：观察组临床控制率为95％;对照组为85％,两组治疗前后实验室数据比较有显著差异（P〈0．01）。结论：自拟益肾汤治疗早期糖尿病肾病,能显著降低血糖,保护肾脏,具有显著效果,值得临床使用。     

大鼠肾脏细胞17β-HSD1的表达及参与性激素合成的能力

目的通过研究合成性激素的关键酶17β-HSD1在肾脏中的表达,探讨肾脏是否具备合成性激素的作用。方法基于无促
卵泡生成素（FSH）、黄体生成素（LH）培养基和有FSH、LH培养基两种条件下,Western blotting、放射免疫分析法分别检测培
养24、48 h 后肾脏细胞中17β-HSD1 的表达和性激素的分泌情况。结果培养24 h 后,大鼠肾脏细胞能够表达少量的
17β-HSD1 蛋白（0.1843±0.076）,同时能够分泌少量的雌二醇、孕酮和睾酮（分别为3.30±3.78 nmol/L,62.60±12.33 pmol/L 和
22.12±3.36 nmol/L）,而在FSH和LH的共同刺激下,大鼠肾脏细胞17β-HSD1蛋白的表达量明显升高（1.6651±0.044,P<0.01）,
同时分泌雌二醇、孕酮和睾酮的量也显著增加（分别为8.50±2.64 nmol/L,117.80±9.79 pmol/L和45.04±4.39 nmol/L,均P<0.05）,
培养24 h和48 h上述指标均无明显差异（P>0.05）。结论大鼠肾脏细胞中有17β-HSD1的表达,并且在FSH和LH的共刺激下
能够稳定分泌性激素,提示肾脏组织具备合成性激素的能力,丰富了肾脏的内分泌功能。
     

Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.     

The effect of fluid intake on renal length measurement in adults

PURPOSE: To evaluate whether oral fluid intake has an effect on renal length as determined with sonography. METHODS: We studied 524 adult patients who were referred to our ultrasound unit with complaints other than urinary tract symptoms. The mean age of the patients was 44 years (range 17-76). All of the measurements were performed with the patient in the prone position. The renal length of each kidney was measured by the same observer before and after oral fluid intake. Student's t-test was applied for the statistical significance of renal length measurements before and after hydration. Analysis of variance was performed for the effect of age and sex on the renal length measurements. RESULTS: The mean renal length on the right side was 106.2 +/- 5.5 mm and 107.5 +/- 5.7 mm on the left side before hydration. There was no statistically significant difference between right and left side renal length measurements. After hydration, the mean renal length was 113.5 +/- 6.1 mm on the right side and 114.6 +/- 6.6 mm on the left side. The mean increase in renal length after hydration was statistically significant (P < 0.001) and was 6.8% on the right side and 6.6% on the left side. Sex and age did not affect the measurements significantly. CONCLUSIONS: Oral fluid intake causes a statistically significant increase in renal length. This observation should be taken into consideration when renal length measurements are clinicallly important.     

Histomorphological assessment of non-neoplastic renal diseases at autopsy: an institutional experience in Southwestern Nigeria

BackgroundAutopsy remains an invaluable resource for medical education and establishing diagnosis of diseases that were missed prior to death. Many patients on admission in hospitals suffer kidney diseases that may contribute to their morbidity and/or mortality. The kidneys from autopsies provide opportunity to diagnose and understand some of these non-neoplastic renal lesions. This study aimed to present the frequency of non-neoplastic renal diseases at autopsy.MethodsWe conducted a five-year retrospective review of post-mortem records of deceased who had autopsy. Data such as age, sex, cause of death, and kidney lesions were extracted from the post-mortem records and clinical details were gotten from the clinical summaries in the autopsy reports. The kidneys were examined for pathological findings that were then classified into glomerular, tubulointerstitial (tubulointerstitial nephritis and other tubular lesions such as tubular necrosis, casts and fibrosis) and vascular lesions.ResultsA total of seventy (70) cases met the inclusion criteria with 91.4% having significant non-neoplastic renal lesions. The mean age of the deceased was 57.7years (18years – 91years). Males accounted for 65.7% of the cases. Glomerular lesions were seen in 84.3% of the cases, tubulointerstitial nephritis in 41.6% of cases, vascular lesions were seen in 30% of the cases and other tubular lesions (such as stones, casts and tubular necrosis) were seen in 52.9% of the cases. Cardiovascular diseases and infections were the major causes of death in these patients, accounting for 40% and 27% respectively. Renal diseases were attributed to immediate cause of death in 10% of the cases.ConclusionThe kidney at autopsy provides a valuable renal pathology educational tool, as a wide range of medical renal lesions can be seen from kidneys examined at post mortem.