聚丙交酯/乙交酯胆道支架生物降解及与宿主的相容性

背景：胆道支架广泛应用于不同的胆道疾病的外科治疗中,但目前使用的胆道支架存在一定的缺陷。 目的：探讨聚丙交酯/乙交酯胆道支架的生物降解性和相容性。 方法：制备聚丙交酯/乙交酯胆道支架,浸入胆汁中,浸泡后1,2,3,4,5周,分别取8个实验支架干燥处理后置于扫描电镜下进行观察。于无菌条件下将实验支架植入大鼠皮下,分别于植入后1,2,3,4,5周,处死2只,将实验支架取出,观察支架外观及实验动物周围肌肉组织情况。观察不同时间的支架大体外观和电镜扫描情况,计算降解率,并了解实验动物肌肉埋植情况和支架情况。 结果与结论：植入后1周支架外形基本保持完整,但质地变软,之后逐渐出现表面粗糙并存在裂痕,支架管壁出现塌陷,植入后5周支架被完全降解。降解前,实验支架经扫描电镜观察呈现出清晰的三维立体网状结构,随着实验时间的不断延长,支架表面和截面腐蚀现象不断加重。经凝胶渗透色谱仪检测发现,植入后1周,支架相对分子质量出现迅速的下降现象,之后渐保持平缓下降状态。植入后2周检测,相对分子质量下降为15 000;植入后4周,支架质量损失约40%;所有实验动物均成活,未出现中毒和过敏以及热源反应等,手术伤口均良好愈合,未发生感染。经组织学观察,植入后5周,支架被完全降解,降解率为100%,周围肌肉组织恢复至正常状态。结果表明,聚丙交酯/乙交酯胆道支架具有良好的体外降解性以及生物相容性。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Platelet activation marker

Atherosclerosis is the leading cause of death in patients with diabetes mellitus, increasing mortality in all forms of the disease. Classical risk factors, including hyperlipidemia, hypertension and obesity, do not completely account for the increased incidence of atherosclerosis in diabetes. Some platelet activation markers such as CD62P, CD63, PAC-1, Annexin V and platelet-derived microparticles (PDMP) are elevated in patients with diabetes, since diabetic platelets often have increased sensitivity to secondary aggregation in response to agonist. PDMPs are thought to play a role in clinical disease because they express phospholipids that function as procoagulants. High shear stress can initiate both platelet aggregation and shedding of procoagulant-containing PDMP, suggesting that PDMP generation by high shear stress occurs in small diseased arteries and arterioles under various clinical conditions. Platelet activation markers were significantly higher in the hypertensive or hyperlipidemic patients than in the controls. Selectins and cell adhesion molecules were also higher in the hypertensive or hyperlipidemic patients, and they were significantly higher in these patients with diabetes. Activated microparticles and PDMP may contribute to the development of atherosclerosis in diabetes, and platelet activation markers seem to be useful for the assessment of vascular damage in these patients.     

Platelet influence on T- and B-cell responses

Understanding the adaptive immune response is an area of research critically important in medicine. Several positive regulators of B- and T-cell activation exist to eliminate pathogens, in which CD40 ligand (CD154) plays a fundamental role. It is well documented that CD154 expressed by CD4 T helper cells can be critical in the proper activation of dendritic cells for the productive stimulation of CD8 T cells and is required for proper T-dependent B-cell immunity. However, platelets are an abundant and systemic source of CD154. While classically known to be important for hemostasis and inflammation, several lines of evidence suggest that platelet-derived ligands can modulate the adaptive immune compartment.     

Platelet and coagulation factors in proliferative diabetic retinopathy.

Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.     

Platelet activating factor and endotoxin-induced platelet activation

Central Research Institute of Epidemiology, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. I. Pokrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 5, pp. 538–540, May, 1989.     

Platelet activation and PDGF-AB release during dialysis

During hemodialysis the blood-membrane contact causes a release of platelet granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG and MPV levels were determined in the peripheral blood in 30 patients each of whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane. Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis sessions and at 1, 4 and 20 hours after the end of the session. Statistical analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum levels initially increased and, except for a sharp fall at 120', remained constantly high during HD with both membranes tested, not returning to basal values until 20 hours after the end of the session. PF4, betaTG and MPV all showed a similar trend to PDGF. No statistically significant difference was found between the two membranes tested. PDGF-AB, a powerful growth factor in cells of mesenchymal origin, is released during dialysis mainly as a result of the blood-membrane contact. This we found regardless of the type of dialyzer we tested, and, above all, proved to return very slowly to basal values. We speculate that the release of PDGF-AB could play a part like other atherosclerosis risk-factors in the appearance and worsening of atherosclerotic lesions in hemodialysis patients.     

Platelet adhesiveness, coagulation, and fibrinolytic activity in obesity

In a study of 41 fasting subjects it was confirmed that fibrinolytic activity was reduced in obese persons: an increase in fibrinogen was also associated with obesity. There was no correlation between obesity and the platelet count, platelet adhesiveness to glass, the level of serum fibrin degradation products, or the whole blood clotting time in plastic tubes.     

Platelet responses to silicon-alloyed pyrolytic carbons

Pyrolytic carbon (PYC) containing approximately 7 wt % silicon is used in most clinical mechanical heart valves where it has demonstrated a high level of blood compatibility. The Si, present as SiC, is included since it is believed to enhance durability. However, it has been suggested that SiC reduces PYC blood compatibility. In the present study, PYC valve leaflets were prepared with low, conventional, and high levels of Si. The in vitro responses of human platelets to these materials were then quantified. Platelet responses were consistent with previous reports: Adherent platelets were extremely well spread, closely followed submicron contours, and formed very few aggregates or microthrombi-like structures. No significant differences with respect to the Si concentrations were observed for platelets adherent per unit area and the numbers of thrombi-like structures. Some differences were observed with platelet morphologies and the material surface covered with platelets, although these did not vary consistently with respect to Si concentration. These results indicate that lowering (or raising) the Si alloy concentration in PYC over a reasonable range (0.54-13.5 wt % as examined here) is unlikely to improve or otherwise alter the in vivo blood compatibility of this important clinical material.     

Platelet activation in unstable coronary disease

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.     

Automatic detection of stent struts with thick neointimal growth in intravascular optical coherence tomography image sequences

To assist cardiologists investigating neointimal tissue growth on stents during follow-up with optical coherence tomography (OCT), we developed an automatic algorithm to locate deeply buried stent struts and to quantify the restenosis burden. The technique is based on an improved steerable filter for computing the local ridge strength and orientation. It also uses an ellipsoid fitting algorithm and continuity criteria to obtain globally optimal stent localization. The restenosis burden calculations were compared to manual assessment of OCT coronary artery image data obtained from in vivo human clinical studies. Compared to manual assessment by expert readers, the algorithm operated with >?97% accuracy in the measurement of mean and maximum restenosis burden. The results indicated that the technique yielded comparable accuracy in measuring restenosis burden, and significantly reduced user interaction time.     

Platelet antistaphylococcal responses occur through P2X1 and P2Y12 receptor-induced activation and kinocidin release

Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of ≥10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5′-phosphonucleotide derivative (a specific P2X₁ antagonist), and cangrelor (a specific P2Y₁₂ antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A₂, cyclooxygenase-1/cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X₁/P2Y₁₂ receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs.     

Platelet adhesion and activation on a shielded plasma gradient prepared on polyethylene.

Contact of blood with foreign materials evokes thrombogenic effects to an extent determined partly by the wettability of the biomaterials surface. Tools to study blood response towards a variation in materials wettability with minimal variation in chemistry are "gradient surfaces". However, most gradients have been prepared by diffusion or density immersion techniques, which results in a limited gradient range. Through glow discharge with partial shielding, gradients on polymers were prepared over a length of 5 cm, which facilitated studies to platelet adhesion on separate gradient sections. On polyethylene, advancing water contact angles varied from 90 degrees to 40 degrees, with a hysteresis of 30 degrees. ESCA indicated an increasing incorporation of oxygen towards the hydrophilic end. To examine the role of materials wettability on the activation of adhering platelets, sections of shielded plasma gradients were incubated in anticoagulated whole human blood. Fewer platelets adhered to the hydrophobic end, but those platelets were more activated than those on the hydrophilic end, as judged from their morphology and exposure of GpIIb-IIIa complex. However, partly related to the increased binding of platelets, the clotting activation after platelet deposition was highest on the hydrophilic end. Concluding, this new technique results in a large gradient range, which facilitates studies of formed blood elements in relation to the wettability. Platelets are more activated on hydrophobic polyethylene, while on moderate hydrophilic polyethylene more platelet adhesion and activation of the clotting system occurs.     

Platelet activation by low density lipoprotein and high density lipoprotein

Cardiovascular disease is the main cause of death and disability in the Western society. Lipoproteins are important in the development of cardiovascular disease since they change the properties of different cells involved in atherosclerosis and thrombosis. The interaction of platelets with lipoproteins has been under intense investigation. Particularly the initiation of platelet signaling pathways by low density lipoprotein (LDL) has been studied thoroughly, since platelets of hypercholesterolemic patients, whose plasma contains elevated LDL levels due to absent or defective LDL receptors, show hyperaggregability in vitro and enhanced activity in vivo. These observations suggest that LDL enhances platelet responsiveness. Several signaling pathways induced by LDL have been revealed in vitro, such as signaling via p38 mitogen-activated protein kinase and p125 focal adhesion kinase. High density lipoprotein (HDL) consists of two subtypes, HDL(2) and HDL(3), which have opposing effects on platelet activation. This review provides a summary of the activation of signaling pathways after platelet-LDL and platelet-HDL interaction, with special emphasis on their role in the development of thrombosis and atherosclerosis.     

Platelet and leukocyte activation and design consequences for thoracic artificial lungs

Blood contact with the prosthetic surfaces of artificial lungs causes extensive activation of molecular and cellular mediators of coagulation and inflammation that can lead to patient morbidity and mortality. To determine the effects of artificial lung fiber bundle shear stress and surface area on blood activation, porcine blood was recirculated for 4 hours through circuits containing mock artificial lungs with bundle shear stresses of 11.6, 7.3, and 3.9 dynes/cm2 and surface areas of 5.2, 3.5, and 1.7 cm2/ml of circuit volume. Blood from these circuits was assayed for platelet and leukocyte counts, soluble P-selectin concentrations, and lactoferrin concentrations to determine the level of platelet and leukocyte adherence to the circuit, platelet activation, and leukocyte activation, respectively. Neither platelet nor leukocyte counts were significantly affected by shear stress or surface area. P-selectin and lactoferrin concentrations were significantly greater at a fiber bundle shear stress of 11.6 dynes/ cm2. P-selectin and lactoferrin concentrations were significantly greater at a fiber bundle surface area of 5.2 cm2/ml of circuit volume. Artificial lungs, therefore, should be designed with average bundle shear stresses < 11.6 dynes/cm2 and with surface areas < 5.2 cm2/ml of circuit volume. Current thoracic artificial lungs meet both these requirements.