Multimodal SPION-CREKA peptide based agents for molecular imaging of microthrombus in a rat myocardial ischemia-reperfusion model

Microthrombosis plays a key role in many cardiovascular diseases. Although it is not difficult to localize thrombus within large or middle-sized vessels, the noninvasive diagnostic regimen for the detection of microthrombus remains scarce. Here we developed a nanoagent by conjucting superparamagnetic iron-oxide nanoparticle with fluorophore and a targeting element, CREKA, a peptide with special affinity for fibrin. In a rat model of myocardial ischemia–reperfusion (MI/R), the multimodal nanoagents were readily and selectively accumulated within microthrombosis, which was detectable by both magnetic resonance and optical imaging modalities. The fibrin-targeted nanoagent could be expected to have utility not only in molecular imaging of fibrin, understanding the mechanisms of microcirculation disorders, but also in targeted therapy with fibrinolytic agents.     

Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses

Mast cell activation has been shown to be an initiator and a key determinant of foreign body reactions. However, there is no non-invasive method that can quantify the degree of implant-associated mast cell activation. Taking advantage of the fact that fibrin deposition is a hallmark of mast cell activation around biomaterial implants, a near infrared probe was fabricated to have high affinity to fibrin. Subsequent in vitro testing confirmed that this probe has high affinity to fibrin. Using a subcutaneous particle implantation model, we found significant accumulation of fibrin-affinity probes at the implant sites as early as 15 min following particle implantation. The accumulation of fibrin-affinity probes at the implantation sites could also be substantially reduced if anti-coagulant – heparin was administered at the implant sites. Further studies have shown that subcutaneous administration of mast cell activator – compound 48/80 – prompted the accumulation of fibrin-affinity probes. However, implant-associated fibrin-affinity probe accumulation was substantially reduced in mice with mast cell deficiency. The results show that our fibrin-affinity probes may serve as a powerful tool to monitor and measure the extent of biomaterial-mediated fibrin deposition and mast cell activation in vivo.     

The use of D-dimer in specific clinical conditions: A narrative review

The use of D-dimer in combination with a clinical decision rule has been widely investigated in pulmonary embolism and deep venous thrombosis. Although it has been shown to be safe in excluding venous thromboembolism, the clinician is often faced with specific situations in which the use of D-dimer is controversial. We review the best available evidence on these patients. We conclude that it is not safe to use D-dimer testing in patients with symptoms of a venous thromboembolism for over 14 days, patients receiving therapeutic heparin treatment and patients with suspected deep venous thrombosis during oral anticoagulant therapy. In these populations the levels of D-dimer can be lower then expected giving rise to false-negative results. It is safe to use D-dimer testing in combination with a clinical decision rule in patients of all ages, patients presenting with a suspected recurrent venous thromboembolism or inpatients with suspected pulmonary embolism. As patients with recurrent venous thromboembolism, elderly patients and inpatients have higher levels of D-dimer, D-dimer testing has a low specificity and the need for additional radiological testing is increased.     

纤维蛋白封闭剂治疗妊娠中晚期胎膜早破的护理

目的探讨纤维蛋白封闭剂治疗妊娠中晚期胎膜早破的有效护理措施,提高治疗安胎成功率。方法对8例采用纤维蛋白封闭剂治疗妊娠中晚期胎膜早破孕妇采取针对性的术前准备,术后护理、预防感染、严密监护胎儿宫内安危,合理的出院指导等护理措施。结果8例患者经纤维蛋白封闭剂治疗后,均成功产下成活新生儿;5例术后痊愈出院,至足月后入院正常分娩,3例术后一直住院安胎,后行剖宫产。结论妊娠中晚期胎膜早破严重危害母婴安全,纤维蛋白封闭剂对妊娠中晚期胎膜早破有较好的治疗效果,应根据不同孕妇的具体情况采取有针对性的护理措施。     

内瘤变创口愈合的影响

目的研究医用生物蛋白胶对子宫颈电热圈环切术（100pelectrosurgicalexcisionprocedure，LEEP）治疗宫颈上皮内瘤变，术后创口愈合的影响。方法选择符合诊断和手术条件的宫颈上皮内瘤变患者128例，分治疗组82例和对照组46例，均用LEEP治疗，术后创口分别敷用医用生物蛋白胶和无菌纱布，观察两组并发症（创面感染、肉芽生长、脱痂期出、宫颈管狭窄）发生率，阴道持续出血时间和出血量及创面愈合时间，术后2年疗效及复发率，并进行统计分析。结果两组的并发症发生率分别为2．44％和15．22％，阴道出血持续时间≤2周、〉2周而≤3周、〉3周而≤5周、≥5周的发生率分别为78．05％、23．91％、19．51％、50．00％和2．44％、17．39％、0．00％、8．70％，阴道出血量≤20ml、21～49ml、≥50ml的发生率分别为78．05％、34．78％、21．95％和52．17％、0．00％、13．04％，创面愈合平均时间分别为12．1±5．3天和18．4±4．8天，术后2年随访有效率分别为98．78％和86．96％，两组间比较均有显著差异（P〈0．05）。结论医用生物蛋白胶可促进LEEP治疗宫颈上皮内瘤变创口的愈合，减少并发症，提高治愈率。     

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)