Glomerular Capillary Hemorrhage Induced in Rats by Diagnostic Ultrasound with Gas–Body Contrast Agent Produces Intratubular Obstruction

Glomerular capillary hemorrhage (GCH) induced by ultrasonic cavitation during diagnostic imaging represents a unique contrast agent–related nephron injury. Consequences of GCH during 1.5-MHz diagnostic ultrasound with contrast agent were examined by histologic methods in rats. Definity was infused at 10 μl/kg/min for 5 min at the start of 8 min of intermittent image-exposure, with 2.3 MPa in situ peak rarefactional pressure amplitude. Kidney samples were taken for histology at 5 min, 30 min, 4 h, 2 d, 1 week and 4 weeks post exposure. In addition, samples were taken at 4 h from groups treated with heparin or aminocaproic acid. GCH was found in 61% of glomeruli in the center of the scan plane 5 min after exposure, which declined (p < 0.05) to 36.3% after 4 h. The width of Bowman's space was significantly increased for glomeruli with GCH relative to glomeruli without GCH (p < 0.05), consistent with tubular obstruction. Antibody staining revealed fibrin clotting in Bowman's space in 4-h samples and this persisted in the 2-d samples. Heparin reduced and aminocaproic acid increased the GCH seen in 4-h samples. Tubular dilation was evident with injury to the epithelium after 2 d. After one week, areas of inflammatory cell infiltration were present. After four weeks, areas of interstitial fibrosis were revealed by Masson's trichrome stain. The consequences of GCH induced by diagnostic ultrasound with contrast agents include rupture of glomerular capillaries, procoagulant activity resulting in intratubular obstruction, and the potential for progression of the resulting tubular injury toward interstitial fibrosis. (E-mail: douglm@umich.edu)     

生物蛋白胶联合生长激素对腹腔感染后肠吻合口愈合的影响机制

目的:探讨生长激素(GH)和医用生物蛋白胶(FS)联合应用对腹腔感染肠吻合口愈合的影响机制. 方法:将腹腔感染24 h大鼠随机分为三组:对照组行肠切除肠吻合;FS组行肠切除肠吻合,吻合口喷涂FS;GH组行肠切除肠吻合,吻合口喷涂FS,术后应用GH.观察吻合口组织形态学及纤维连接蛋白(FN)、α-平滑肌肌动蛋白(α-SMA)、血管内皮细胞生长因子(VEGF)表达和细胞凋亡情况. 结果:GH组FN、α-SMA、VEGF表达均显著高于对照组及FS组,术后吻合口细胞凋亡明显低于对照组和FS组. 结论:FS联合应用GH能减轻感染对组织修复起始过程的影响,促进血管内皮细胞增殖及肉芽组织形成,促使成纤维细胞向肌成纤维细胞分化,且α-SMA表达的动态变化过程与肌成纤维细胞凋亡出现的频度呈现出较好的相关性.     

局部应用生物蛋白胶和加替沙星对手及前臂屈肌腱粘连及感染的预防

目的评价生物蛋白胶和加替沙星对肌腱吻合后预防粘连及局部感染的作用。方法12例肌腱断裂患者肌腱吻合后喷涂生物蛋白胶和加替沙星混合剂,观察患指功能恢复及伤口愈合情况,术后随访2~10个月。结果应用生物蛋白胶和加替沙星混合剂的患指功能恢复优良率为83.33%,较好为16.67%。结论生物蛋白胶和加替沙星对肌腱吻合后功能恢复和伤口愈合有良好疗效。     

阿霉素-纤维蛋白胶缓释化疗系统的实验研究

目的探讨医用纤维蛋白胶携载阿霉素(Adriamycin,ADM)的缓释作用。方法体外实验:用纤维蛋白胶(FG)携载ADM,观察ADM体外缓释情况;体内实验:将其注入兔体内,定时采取外周血作为样本,测试样本中的ADM质量浓度,计算外周血中ADM的动力学参数。结果体外释放实验显示,2h后ADM的累积释放率为(30.53±0.56)%,24h后为(42.16±0.86)%,120h后释放趋于平衡。动物实验表明:外周血峰质量浓度(ρmax)实验组显著低于对照组,差异有显著性意义(P<0.01);外周血T1/2和曲线下面积(AUC)实验组均明显高于对照组,差异有显著性意义(P<0.01)。结论在体内外条件下,ADM在生物蛋白胶中均有良好的缓释作用。在兔子肝脏局部使用本制剂,可延长ADM在肝脏的滞留时间,降低其在外周血中的质量浓度。     

Identification of a region of the fibrin molecule involved in upregulation of interleukin-8 expression from human oral squamous cell carcinoma cells

A number of studies have implicated the fibrin-coagulation-fibrinolysis system in human tumour progression. Interleukin-8 (IL-8) mediates most of the angiogenic activity induced by human oral squamous cell carcinoma (OSCC) cells. We have recently demonstrated that: (1) fibrin is present in association with IL-8 expressing human OSCC cells in vivo and (2) in situ fibrin polymerisation induces a specific, dose and time-dependent upregulation of IL-8 expression from human OSCC cells in vitro. Our present studies extend this observation by demonstrating that in addition to fibrin formed in situ, both fibrin-derived liquid expressates (soluble fibrin) and preformed fibrin clots induced an over eight-fold stimulation of IL-8 expression from human OSCC cells as compared to media controls. IL-8 upregulation by soluble fibrin was dose-dependent. A monoclonal antibody against the N terminal region of the beta chain of human fibrin (Bbeta15-42) inhibited 67% of soluble fibrin-induced IL-8 expression from human OSCC cells. A peptide (GHRP), representing the sequence at the N terminus of this region, induced a dose-dependent stimulation of IL-8 expression, further confirming the role of this region. These studies directly support our hypothesis that fibrin induces protumourigenic factor expression from tumour cells, thus promoting tumour progression. Future studies to further characterise the role of the Bbeta15-42 region in tumour cell activation may lead to the design of peptide antagonists with important therapeutic potential.     

Purification of salmon clotting factors and their use as tissue sealants

Fibrin sealant prepared from the blood of farmed Atlantic salmon (Salmo salar) represents a potential source of well-controlled natural material with utility in a variety of clinical settings. A potential advantage of this material is a lower probability of viral or bacterial infection that has limited general approval of fibrin glues made from human or bovine proteins. This report describes the purification of fibrinogen from salmon blood, the use of fibrin glues derived from this material to promote wound healing in rats, and the antigenic response to this material. While the low ambient temperature of these cold water fish significantly lessens the probability of infectious transmission to humans, fibrinogen and factor XIII derived from S. salar are activated by human thrombin at 25°C and 37°C to form clots equivalent to those formed by human fibrin. We compare the reactivity of salmon and human fibrinogen with human and bovine thrombin and the structure and viscoelastic properties of the resulting fibrin gels over a range of pH and salt concentrations. The efficacy of salmon fibrin glues in a wound healing assay and the low antigenic response to salmon fibrinogen suggest that this material may substitute for proteins derived from mammalian sources with lower probability of infections.     

Endoluminal embolization of bilateral atherosclerotic common iliac aneurysms with fibrin tissue glue (Beriplast)

The standard surgical approach to nonleaking iliac aneurysms found at repair of a leaking abdominal aortic aneurysm is to minimize the operative risk by repairing the abdominal aorta only. This means that the bypassed iliac aneurysms may have to be repaired later. As this population of patients are usually elderly with coexisting medical problems, interventional radiology is being used to embolize these aneurysms, thus avoiding the morbidity and mortality associated with further general anesthesia and surgery. Various materials and stents have been reported to be effective in the treatment of iliac aneurysms. We report the successful use of endoluminal fibrin tissue glue (Beriplast) to treat two large iliac aneurysms in a patient who had had a previous abdominal aortic aneurysm repair. We discuss the technique involved and the reasons why we used tissue glue in this patient.     

纤维蛋白胶外周支持对大鼠颈静脉移植物内膜的影响

目的探讨纤维蛋白胶可降解血管外周支持对静脉移植物急性期内膜的影响。方法建立大鼠颈总动脉自体颈静脉移植模型,按照有无纤维蛋白胶血管外周支持,分为纤维蛋白胶外周支持组、无外周支持组,每组24只大鼠。移植术后2小时切除移植静脉,进行扫描电镜检查,用Ⅷ因子染色的方法检测内皮的缺失情况。结果Ⅷ因子染色显示,纤维蛋白胶外周支持组的静脉移植物内皮层基本保持完整,而无外周支持组的静脉移植物内皮层破坏严重。扫描电镜检查显示,纤维蛋白胶外周支持组的静脉移植物内膜大致结构正常,无外周支持组的静脉移植物血管内膜结构破坏严重。结论纤维蛋白胶血管外周支持,能够改善静脉移植物的应力状态,减轻动脉循环引起的急性机械性损伤,保持血管内皮层的完整性。     

纤维蛋白胶复合BMP治疗兔股骨头缺血性坏死的实验研究

【目的】通过局部植入骨形态发生蛋白（BMP），探索股骨头缺血性坏死早期治疗的新方法。【方法】连续肌肉注射地塞米松制造股骨头缺血性坏死（ANFH）的动物模型，将实验动物分为A，B，C3组，于股骨头下钻孔，在A组和B组分别将BMP／FS或单纯的BMP植入孔道，C组作为空白对照。通过大体观察、MRI检查、钙含量测定和组织学观察，研究复合材料对ANFH的修复作用。【结果】MRI观察显示，植入BMP／FS8周后原骨缺损孔道消失，被新生骨所取代。单纯植入BMP可见少量新生骨，空白对照组内仍为纤维组织。A组钙含量显著高于另外两组。组织形态学观察可见A组术后8周原骨缺损区基本消失，有大量相对较成熟的骨小梁及板状骨并存。B组骨缺损区明显缩小，周边亦有少量骨小梁存在，新生毛细血管少见，缺损区有大量纤维组织填充。C组术后8周缺损区缩小，周边有少量新骨形成并逐渐形成骨壁，中心部仍为纤维组织，无骨组织充填。【结论】BMP在缺血坏死的股骨头内可诱导新骨形成，与FS复合后，BMP诱导新骨形成的质量和数量均明显提高，局部植入BMP／FS对ANFH具有良好的修复作用。     

Hemostasis for the Ramstedt procedure: Use of a fibrin adhesive

Pre- and postoperative blood counts were retrospectively compared between patients with no hemostatic management (group A,n = 30) and patients with a fibrin adhesive (Beriplast P) applied to the cut edges (group B,n = 8) when pyloromyotomy was performed for hypertrophic pyloric stenosis. Postoperative red blood cell count, hematocrit, and hemoglobin were significantly decreased in group A (P <0.01) while there was no significant change in group B. It has been stated that the Ramstedt operation does not require any special hemostatic management. However, as postoperative peritoneal bleeding is suspected, hemostatic management with a fibrin adhesive applied to the incised region of the serosa and muscle layer is recommended.