A comparison of the avascular capsule surrounding free floating intraperitoneal blood clots in mice and rabbits

The development of the avascular fibrous capsule which surrounds free floating intraperitoneal blood clots in mice and rabbits is described. In mice, the capsule at 2 wk consisted of an outer layer of partially flattened macrophage-like cells overlying a thick layer of myofibroblasts embedded in a collagenous stroma. In contrast, in rabbits the capsule at 2 wk consisted of 3 distinct layers: an outer layer of mesothelial cells; an underlying relatively acellular layer containing a few macrophages; and, immediately adjacent to the clot, an innermost layer of variable thickness consisting mostly of myofibroblasts. The myofibroblasts of the rabbit capsule were fewer in number than those of the mouse. Detailed examination of the formation of these capsules suggests that myofibroblasts may develop from cells within the peritoneal cavity that show morphological features characteristic of monocytes/macrophages.     

A model for the formation and lysis of blood clots

Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183-218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.     

CT静脉造影术可增加对静脉血栓风险的发现

放射医学杂志于2月份发表的一项研究指出,对下肢进行计算机成像技术(CT)扫描可预防肺部复发性血栓的发生.该研究发现间接CT静脉造影(CTV)可证实是否存在潜在脱落风险的下肢血栓,后者可随着血流到达肺动脉血管,形成至命的肺栓塞.肺栓塞和下肢血栓形成(也称深部静脉血栓形成),均是以血栓栓塞为主要表现的疾病.CT肺血管造影(CTPA)是肺部扫描的技术之一,常常用于检测肺部是否存在血栓.由于许多小血管中的血栓不能被该检查发现,因此有些病人的血栓性疾病并不能得到诊断.间接CTV可能有助于发现这类血栓形成.“许多研究显示仅治疗与复发性肺…     

An apparatus for measuring the tensile strength of blood clots

An apparatus is described which uses the principle of the ballistic pendulum to measure the tensile strength of blood clots formed in special cuvettes. The method appears to have a reproducibility which would allow a study to be made of the factors influencing clot strength. A brief survey of the findings with normal blood and with blood from cases of thrombosis and haemophilia shows significant differences between the mean values for each group.     

Modelling the effect of laminar axially directed blood flow on the dissolution of non-occlusive blood clots

Axially directed blood plasma flow can significantly accelerate thrombolysis of non-occlusive blood clots. Viscous forces caused by shearing of blood play an essential role in this process, in addition to biochemical fibrinolytic reactions. An analytical mathematical model based on the hypothesis that clot dissolution dynamics is proportional to the power of the flowing blood plasma dissipated along the clot is presented. The model assumes cylindrical non-occlusive blood clots with the flow channel in the centre, in which the flow is assumed to be laminar and flow rate constant at all times during dissolution. Effects of sudden constriction on the flow and its impact on the dissolution rate are also considered. The model was verified experimentally by dynamic magnetic resonance (MR) microscopy of artificial blood clots dissolving in an in vitro circulation system, containing plasma with a magnetic resonance imaging contrast agent and recombinant tissue-type plasminogen activator (rt-PA). Sequences of dynamically acquired 3D low resolution MR images of entire clots and 2D high resolution MR images of clots in the axial cross-section were used to evaluate the dissolution model by fitting it to the experimental data. The experimental data fitted well to the model and confirmed our hypothesis.     

Influence of blood clots in the cumulus complex on oocyte fertilization and cleavage

Since multiple ovarian punctures are performed during oocyteretrieval, the likelihood of blood contaminating the follicularfluid is high. The purpose of this study was to determine whetherthe presence of blood clots, which are frequently seen in thecumulus of oocytes retrieved under ultrasound guidance, hasany effect on fertilization and subsequent embryo cleavage andto identify oocyte characteristics which may predict these events.Oocytes were morphologically graded and the presence of bloodclots in the cumulus was recorded. Cases in which the male partnerhad a total motile sperm count < 20 ? 10⁶ on the day of inseminationwere excluded from the logistic regression analysis. The presenceof blood clots in the cumulus was a negative predictor of cleavage[odds ratio (OR) = 0.54]. The results indicate that an oocytewith optimal quality is one which is spherical (OR = 5.45),has an expanded corona (OR = 3.80) and has no blood clots inthe cumulus complex.     

Zeroing in on the root cause of the clots in a blood bag: Reinforcing improvement in blood collection practices

Blood clots in the packed red blood cell [PRBC] unit can sometimes go unrecognized and could eventually give rise to flow problems while administering the same. We herein report our observation of a moderately elongated threadlike clot in a PRBC unit prepared from a whole blood donated by a young Indian male donor. The PRBC unit was returned to us from the ward by the nursing staff citing “flow issues”. In fact, this warranted the initiation of root-cause analysis of the entire event led by two faculty members, one post-graduate student and the technical supervisor at our blood centre.     

骨蚀宁胶囊对激素性股骨头坏死模型兔凝血机制的影响☆

背景：骨蚀宁胶囊是丁锷教授在长期治疗激素性股骨头缺血性坏死的临床实践中,总结出的有效方剂。 目的：观察骨蚀宁胶囊对激素性股骨头坏死动物模型相关凝血指标的影响。 方法：随机选取6只白兔为正常对照组,余90只白兔利用大肠杆菌内毒素加甲强龙的方法成功制备兔激素性股骨头坏死的动物模型后随机分为骨蚀宁低剂量组[0.47 g/(kg•d)]、中剂量组[1.41 g/(kg•d)]、高剂量组[4.23 g/(kg•d)]及模型组和对照组[仙灵骨葆1.92 g/(kg•d)],分别于用药后4,8,12周检测各项指标。 结果与结论：模型组各时段血浆血栓素B2、GMP-140和血栓调节蛋白水平与均显著高于其他组,6-keto-PGF1α显著低于其他组(P < 0.01,或P < 0.05)。随骨蚀宁治疗时间的延长,血栓素B2、GMP-140和血栓调节蛋白水平逐渐降低6-keto-PGF1α水平逐渐升高;中剂量组较低、高剂量组及对照组作用更加明显(P < 0.01,或P < 0.05)。提示1.41 g/(kg•d)剂量骨蚀宁胶囊改善兔股骨头局部组织瘀血状态,防治激素性股骨头坏死效果较好。     

Comparison of fibrin clots derived from peripheral blood and bone marrow

Background: Autologous fibrin clots derived from peripheral blood (pb-fibrin clot) and bone marrow (bm-fibrin clot) are thought to be effective for tissue regeneration. However, there is no report detailing the amount of growth factors in pb-/bm-fibrin clot. In this study we evaluated the amount of growth factors in human pb-/bm-fibrin clot, and prove the validity of fibrin clot for clinical use. Methods: Human pb-/bm-fibrin clots were obtained during surgery. In the first experiment, enzyme-linked immunosorbent assay (ELISA) was performed for detecting the amount of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor basic (bFGF), hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-β), platelet derived-growth factors-AB (PDGF-AB), and stromal cell-derived factor-1 (SDF-1). In the second experiment, the efficacy of fibrin clot on the osteogenic differentiation and fibroblast proliferation was evaluated. Pb-/bm-fibrin clots were incubated in human osteoblast derived from mesenchymal stromal cells (MSCs) or human skin fibroblast. Alizarin red staining and real-time PCR (COL1A1, RUNX2) were performed for the detection of osteogenic potential. Cell-growth assay (WST-8) and real-time PCR (COL1A1) were also performed for the detection of the potential of fibroblast proliferation. Results: ELISA analysis revealed that the amount of VEGF, HGF, bFGF, IGF-1, and SDF-1 of bm-fibrin clot group is higher than that of pb-fibrin clot group with statistical differences. Besides, we confirmed that bm-fibrin clot has much potential for the osteogenic differentiation and fibroblast proliferation. Conclusion: The positive outcomes confirm the efficacy of pb-/bm-fibrin clot, and bm-fibrin clot was proved to have much potential for tissue regeneration compared with pb-fibrin clot. The current study showed the potential of a strategy for regenerative medicine using bm-fibrin clot.     

Origin and distribution of portal blood in the sheep

In sheep, the gastrosplenic and mesenteric veins converge at an angle of about 140° to form the portal vein, which is joined, along its right ventral border, by the gastroduodenal vein. At the porta, right and left branches of the portal vein diverge at an angle of 65–70° to supply separate areas that join along a line between the fossa for the gall bladder, and the middle of the left branch. Right dorsal branches leave the portal vein or its right branch near the point of bifurcation. When ¹³¹I-albumin that had been heated was injected into the right ruminal vein and entered the portal stream in the gastrosplenic vein, no significant differences existed in the levels of radioactivity between the areas supplied by the different portal branches. When the ¹³¹I-albumin entered the portal stream from either the gastroduodenal or mesenteric veins, the area supplied by the right branch contained a significantly higher level of radioactivity than the remainder of the liver. When corrections were made for an unequal distribution of blood, it was found that blood from the gastrosplenic vein was distributed preferentially to the left branch, blood from the gastroduodenal vein to the right branch, and that blood from the mesenteric vein enters the right and left branches in preference to the right dorsal branches of the portal vein.     

不同剂量骨蚀宁胶囊对兔激素性股骨头坏死微循环的影响

背景：骨蚀宁胶囊方是安徽中医学院丁锷教授在长期治疗激素诱导股骨头缺血性坏死的临床实践中,根据“结者散之,留者攻之”,“损其有余,补其不足”和“活血、祛瘀、生新”等理论,治疗股骨头缺血性坏死的有效方剂。 目的：观察骨蚀宁胶囊对激素性股骨头坏死模型兔微循环的影响。 方法：随机选取6只新西兰大白兔为正常组,另外90只新西兰大白利用大肠杆菌内毒素加甲强龙的方法成功制备兔激素性股骨头坏死动物模型,兔随机分为骨蚀宁胶囊高、中、低剂量组、模型组和仙灵骨葆对照组进行观察。分别于用药后4,8,12周处死,检测血浆内皮素、一氧化氮及观察血管内皮细胞生长因子、组织病理学的变化。 结果与结论：骨蚀宁胶囊和仙灵骨葆均可升高股骨头坏死模型兔的血管内皮素和NO浓度,且组织病理学观察可见骨蚀宁胶囊治疗组与模型组比较,股骨头坏死明显减轻,血管内皮生长因子表达增强,差异有显著性意义(P < 0.01或P < 0.05)。骨蚀宁胶囊各组间比较,中剂量组差异显著(P < 0.01或P < 0.05),更接近正常组数据。说明中剂量骨蚀宁胶囊可以有效地改善激素性股骨头坏死的微循环。     

Origin of blood cells and HSC production in the embryo

Hematopoietic stem cells (HSCs) are capable of self-renewal and differentiation into all blood cell types. During adult life, they reside in the bone marrow in a quiescent state. By contrast, in the growing embryo hematopoiesis is sequentially found in several developmental niches. This review provides an overview of the still controversial contribution of each of these embryonic sites to the final pool of adult HSCs and discusses new insights into the cellular origin and the molecular regulation implicated in the generation of blood progenitor cells. A better understanding of HSC development during ontogeny is essential to develop new strategies to amplify HSCs or to generate them from embryonic stem cells or by somatic cell reprogramming.     

In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents

The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents.     

血管介入法导入自体血栓建立猴局部脑缺血模型

目的：采用血管介入法导入自体血栓，建立猴局部脑缺血动物模型，为脑缺血的相关研究提供创伤小、应用前景大的基础研究平台。 方法： 以12只食蟹猴为实验对象，采用血管介入法从股动脉将微导管超选至大脑中动脉（MCA）M₁分枝，导入自体血栓堵塞MCA。 结果：栓塞后，数字影像血管造影系统下可见M1段以后的血管显影不良；1 h后，CT灌注成像均显示大脑局部血流量和血容量下降，血流平均通过时间延长；48 h后常规CT平扫可见典型的低密度陈旧性局部脑缺血病灶。栓塞后24 h内，取两只动物尸体解剖，大脑切片TTC染色，显示患侧MCA区脑梗病灶；其余动物清醒后，缺血对侧肢体均有不同程度的瘫痪，神经功能评分均＜60分。 结论： 用血管介入法导入自体血栓建立的猴局部脑缺血动物模型，插管和栓塞过程清晰、定位准确、创伤小、并发症少、结果与临床更相似，在脑缺血的相关研究中有着较好的应用前景。     

Development of glia and blood vessels in the internal capsule of rats

We have explored two aspects of internal capsule development that have not been described previously, namely, the development of glia and of blood vessels. To these ends, we used antibodies to glial fibrillary acidic protein (GFAP) and to vimentin (to identify astrocytes and to radial glia) and Griffonia simplicifolia (lectin; to identify microglia and blood vessels). Further, we made intracardiac injections of Evans Blue to examine the permeability of this dye in the vessels of the internal capsule during neonatal development. Our results show that large numbers of radial glia, astrocytes and microglia are not labelled with these markers in the white matter of the internal capsule until about birth; very few are labelled earlier, during the critical stages of corticofugal and corticopetal axonal ingrowth (E15–E20). The large glial labelling in the internal capsule at birth is accompanied by a dense vascular innervation of the capsule; as with the glia, very few labelled patent vessels are seen earlier. After intracardiac injections of Evans Blue, we find that the blood vessels of the internal capsule are not particularly permeable to Evans Blue. At each age examined (P0, P5, P15), blood vessels are outlined very clearly and there is no diffuse haze of fluorescence within the extracellular space, which is indicative of a leaky vessel. There are three striking differences between the glial environment of the internal capsule and that of the adjacent thalamus. First, the internal capsule is never rich with radial glial fibres (vimentin- and GFAP-immunoreactive) during development (except at P0), whereas the thalamus has many radial fibres from very early development (E15–E17). Second, astrocytes (vimentin- and GFAP-immunoreactive) first become apparent in the internal capsule (E20–P0) well before they do in the thalamus (P15). Third, the internal capsule houses a large transient population of amoeboid microglia (P0–P22), whereas the thalamus does not; only ramified microglia are seen in the thalamus. In summary, our results indicate that all three types of glia in the internal capsule are associated closely with the vasculature, suggesting they may play a role in the development of the blood–brain barrier among the vessels in this white matter region of the forebrain.