Professor Bamford's research in the field of biomaterials

Professor Bamford was regarded by many as the greatest British polymer chemist of the twentieth century and when Bam passed away in November 1999 tribute was quite rightly made to his considerable achievements in the field of polymer science. The aim of this paper is to highlight Bam's contribution to biomaterials research that occupied his attention for over 15 years after his official retirement. In particular a review of the synthetic methods employed by Bam for the modification of polymers to improve haemocompatibility and to function as affinity separation membranes for protein purification is presented.     

Surface modification of the polymers present in a polysulfone hollow fiber hemodialyser by covalent binding of heparin or endothelial cell surface heparan sulfate: Flow characteristics and platelet adhesion

The present study addresses the problem of simultaneous surface modification of various polymers, i.e. polysulfone (PSU), polycarbonate (PC), and polyurethane (PU), which constitute the Ultraflux AV 600 S® hollow fibre hemodialyser. An investigation was first made into six different chemical routes aimed at introducing carboxyl groups onto the surface of PSU, PC, and PU model polymers to which heparin (HE) or endothelial cell surface heparan sulfate (ESHS) was covalently bound via the reaction of residual amino groups and a coupling reagent. Carboxyl groups were introduced using three specific reactions based on their nucleophilic or electrophilic introduction into aromatic repeating units of the polymers and three non-specific carboxylation reactions, i.e. UV, heat or redoxactivation via nitrene or radical species. Concentrations of 1-20 nmol COOH groups per cm^-2 led to HE or ESHS surface concentrations corresponding to one or several layers. Two nonspecific carboxylation reactions followed by HE- or ESHS-coupling provided the lowest change in membrane pore structure according to cut off, clearance (urea, phosphate, maltose), ultrafiltration, and diafiltration assessments. In some cases the introduction of excess negatively-charged carboxyl groups and HE improved the flux properties of the modified membranes. The various methods were applied to the dialysis module. Platelet adhesion was not observed in the case of the ESHS-coating of PSU membrane at shear rates of 1050 s^-1, whereas HE and subendothelial matrix showed 56 and 100% coverage, respectively, under similar conditions. The coating of PSU or of other highflux membranes by ESHS appears a promising method for improving membrane properties and to generate biocompatibility characteristics similar to those of natural blood vessels, i.e. inertness to platelet adhesion and no level effects for complement and intrinsic coagulation cascade activation. The ESHS coating may be used without anticoagulants.     

Gas transfer and blood compatibility of asymmetric polyimide hollow fiber

We have fabricated an asymmetric polyimide hollow fiber for use as a membrane oxygenator. A dry/wet phase inversion process has been applied to a spinning process to prepare the hollow fiber. The fiber structure consisted of a complete defect-free skin layer and a porous substructure characterized by the presence of an open-cell structure and macrovoids. The outer diameter was 480 μm with a wall thickness of 50 μm. Transfer rates of O2 and CO2 in the asymmetric polyimide fiber were 2.3 × 10^-5 and 1.1 × 10^-4 (cm³(STP)/(cm²s cmHg)), respectively, which were four times higher than those measured in the polydimethylsiloxane (PDMS) fiber of the presentlyavailable membrane oxygenator. The (QO₂ /Q_N2)selectivity of the polyimide fiber was 4.9, indicating that the surface skin layer is essentially defect-free. The blood compatibility of the polyimide hollow fiber has been evaluated in vitro and in vivo. The polyimide had an excellent blood compatibility when compared with PDMS.     

Trypsinogen Activation Peptides (TAP) in Peritoneal Fluid as Predictors of Late Histopathologic Injury in Necrotizing Pancreatitis of the Rat

The levels of trypsinogen activation peptides(TAP) were quantified by ELISA immunoassay in acutepancreatitis of the rat and compared to the degree oflate histopathological sequelae and exocrine functional impairment 4 and 12 weeks after the acute phaseof the disease. For this purpose acute pancreatitis ofdifferent severity was induced using a suitable ratmodel recently described. Forty five surviving animals were studied. The level of TAP inperitoneal exudate measured 3 and 6 hr afterpancreatitis induction correlated well with the amountof the late histopathological injury at the end of thecorresponding observation period (at 4 weeks after 3 hr: r =0.75, P = 0.003, after 6 hr: r = 0.72, P = 0.005,Pearson; and at 12 weeks after 3 hr: r = 0.86, P =0.0001, after 6 hr: r = 0.84, P = 0.0001, Pearson). A negative correlation of TAP with the impairmentof exocrine function was found only at 4 weeks for thesecretion of total protein (r = –0.76 after 3 hr;r = –0.62 after 6 hr) and for exocrine function (r = –0.67 after 3 hr, r = –0.57 after6 hr), but not at 12 weeks after acute pancreatitis. Nocorrelation with plasma amylase and lipase was found. Weconclude that quantitation of TAP in ascites provides an accurate prediction of late histopathologicsequelae. Pancreatic exocrine function could bepredicted by TAP assay only in the early stage afterpancreatitis induction (eg, four weeks). In later stages of the disease (eg, 12 weeks) remainingpancreatic tissue seems to compensate for any exocrinedeficits that have occurred.     

Bioactivity and Platelet Adhesion Study of a Human Thrombomodulin-Immobilized Nitinol Surface

Nitinol is a newly developed biomaterial that is gaining popularity in many biomedical applications. It has been reported that nitinol would not induce an inflammatory response and repulsion by the immunization after implantation in the human body. Besides, nitinol is a kind of shape memory alloy, which can memorize shapes at different temperatures. This can improve the convenience in surgery. However, nitinol has poor blood compatibility, so that further modification was needed to improve the antithrombogenicity. Human thrombomodulin (hTM), an endothelial-cell-associated glycoprotein, can be considered as a natural potent anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. In this study, the surface of nitinol was pre-activated by utilizing silanization with amino-terminated silane. The incorporated amino groups were available for the subsequent covalent immobilization of hTM by 2,4,6-trichloro-1,3,5-triazine (TCT), the coupling reagent. The surface density of immobilized hTM was determined by the Bradford method. The bioactivity of immobilized hTM and blood compatibility of various nitinol substrates were evaluated by the protein C activation assay and platelet adhesion test. It was observed that the immobilized hTM still had the ability to enhance protein C activation, though its activity was lower than the free hTM in solution. Furthermore, the platelet adhesion test showed that only a few platelets were adhered on the hTM-immobilized nitinol substrate. Therefore, the immobilization of thrombomodulin onto nitinol substrate could improve the blood compatibility of nitinol and might have the potential of application in antithrombogenic medical applications.     

Effect of adsorbent of Riposorber™, a cellulose microparticle with immobilized dextran sulfate,on the serum complement system

Apheresis, using columns of cellulose microparticles with immobilized dextran sulfate, Riposorber?, has been applied to treatment of patients with various diseases, such as hypercholesterolemia and systemic lupus erythematosus. Unfortunately, it has been reported that the apheresis activates the complement system. It might exert unpleasant side effects on patients during lifelong treatment. In this study, the interaction of the serum complement system with cellulose microparticles with immobilized dextran sulfate and its components, nontreated cellulose microparticles and dextran sulfate, were examined in vitro to get some ideas for development of an extracorporeal apparatus which does not give any serious damage to patient blood. The cellulose microparticles with immobilized dextran sulfate reduces both the CH₅₀ and the ACH₅₀. Decrease in CH₅₀ is not due to the classical pathway activation, but to adsorption of C2 or C1 components including C1q. The alternative pathway was not activated by the addition of the dextran sulfate alone to serum, but the addition of non-treated cellulose microparticles to serum activated complement. Form these, decrease in ACH₅₀ is not caused by dextran sulfate on the microparticles, but by the hydroxyl groups of the cellulose microparticles that is the core of the column. For prevention of complement activation, hydroxyl groups remaining after dextran sulfate immobilization should be blocked by further treatment with a reagent that reacts with them, or else dextran sulfate might be immobilized on particles without nucleophiles such as hydroxyl or amino groups.     

Improved cognitive-cerebral function in older adults with chromium supplementation

Abstract

Insulin resistance is implicated in the pathophysiological changes associated with Alzheimer's disease, and pharmaceutical treatments that overcome insulin resistance improve memory function in subjects with mild cognitive impairment (MCI) and early Alzheimer's disease. Chromium (Cr) supplementation improves glucose disposal in patients with insulin resistance and diabetes. We sought to assess whether supplementation with Cr might improve memory and neural function in older adults with cognitive decline. In a placebo-controlled, double-blind trial, we randomly assigned 26 older adults to receive either chromium picolinate (CrPic) or placebo for 12 weeks. Memory and depression were assessed prior to treatment initiation and during the final week of treatment. We also performed functional magnetic resonance imaging (fMRI) scans on a subset of subjects. Although learning rate and retention were not enhanced by CrPic supplementation, we observed reduced semantic interference on learning, recall, and recognition memory tasks. In addition, fMRI indicated comparatively increased activation for the CrPic subjects in right thalamic, right temporal, right posterior parietal, and bifrontal regions. These findings suggest that supplementation with CrPic can enhance cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration.     

络得舒方的抗炎机理探讨

本文探讨了络得舒方的抗炎机理。实验结果,络得舒方对摘除肾上腺大鼠甲醛性足肿胀仍有明显抑制作用(P<0.05～0.01);对正常大鼠肾上腺内VitC含量无明显影响(P>0.05);对热诱导所致红细胞溶解有明显抑制作用(P<0.01);对妊娠大鼠离体子宫的自发性收缩有明显抑制作用(P<0.01);对二磷酸腺苷所致的血小板聚集有明显抑制作用(体内体外用药P值均<0.01)。结果提示:络得舒方的抗炎作用不是主要依赖垂体——肾上腺皮质系统,可能与保护红细胞膜、抑制前列腺素合成酶和/或拮抗前列腺素、抑制血小板聚集有关。     

益气活血片对脑梗塞大鼠血小板膜粘附分子表达的影响

目的 研究益气活血片（主要由当归，益母草，种芎，黄芪等中药组成）对脑梗塞大鼠模型全血血小板膜粘附分子表达的影响。方法 应用流式细胞仪检测脑梗塞大鼠模型全血血小板膜CD41（糖蛋白Ⅱa-Ⅲa受体的亚基）和CD62P（P－选择素）的表达，并与正常组相对照。结果 脑梗塞大鼠模型血小板膜粘附分子的表达较正常组为高（P＜0．01），而益气活血片能明显降低其表达（P＜0．01）。结论 血小板膜粘附分子表达增高是脑梗塞的重要病理特征之一，益气活血片可能通过降低血小板膜粘附分子的表达，从而抑制血小板活化。     

祛瘀消斑胶囊对冠心病血脂及血小板活性的影响

[目的]探讨祛瘀消斑胶囊（主要由水蛭、大黄、海藻、山楂、莪术等中药组成）对冠心病患者血脂及血小板活性的影响。[方法]采用随机单盲法将62例冠心病患者分为对照组（31例）及中药组（31例），对照组予西药常规治疗，中药组加服祛消瘀斑胶囊，观察两组治疗前后血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL－C）及血液活化血小板α颗粒膜蛋白（GMP－140）的含量变化。[结果]祛瘀消斑胶囊治疗10周后，血液GMP－140，血清TC、TG含量均不同程度地下降，与自身治疗前及对照组治疗后比较差异均有显著性（P＜0.05或P＜0.01)；而血清HDL－C则变化不明显（P＞0.05)。[结论]祛瘀消斑胶囊可降低血脂，改善血小板功能，对冠心病的预防与治疗有一定的积极作用。