The fibrinolytic system in neoplasia

During activation of the fibrinolytic system plasminogen is converted to plasmin by tissue plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA is predominantly released from endothelial cells, u-PA primarily by renal parenchymal cells. The activation of plasminogen is regulated by plasminogen activator inhibitor-1 (PAI-1), plasmin is controlled by alpha 2-plasmin inhibitor. The fibrinolytic system is not only involved in the intravascular dissolution of fibrin (thrombi), it also plays a vital role in normal physiologic reproduction, wound repair, angiogenesis, and tissue remodeling. Fibrinolysis is also a vital component in the pathogenesis of neoplastic disease. It is essential in releasing cells from their primary site of origin, providing nutrition for neoplastic cell growth and promoting cell mobility and motility. In neoplastic cells the degradation of the extracellular matrix proteins is facilitated by excessive expression of u-PA, t-PA, and u-PAR. In many forms of carcinoma increased expression of u-PAR and u-PA is associated with significantly shorter survival. Greater expression of u-PA in breast cancer cells, for example, is associated with shorter survival and increased relapse rate. Progressively aggressive neoplastic cells evidence high expression of u-PA and u-PAR activities, variable expression of t-PA, and enhanced PAI-1 and PAI-2 activities. In acute nonlymphocytic leukemias, poor outcome correlates with high t-PA levels. In acute progranulocytic leukemia there is a high incidence of DIC. Neoplastic prostatic tissue also expresses high u-PA activity and the more aggressive the cell line, the greater the number of u-PAR and the higher the u-PA activity. In gynecologic malignancies, a greater expression of u-PA in combination with cathepsin D is associated with widespread disease and poor prognosis. High u-PA values were also seen in patients with brain, gastric, and hepatic malignancies. It is evident that the plasminogen-plasmin system is a vital component in the biology of neoplastic disease and that it is, in theses conditions, in no way beneficial to the host.     

Definition of the specific roles of lysolecithin and palmitic acid in altering the susceptibility of dipalmitoylphosphatidylcholine bilayers to phospholipase A2

Bilayers composed of phosphatidylcholine initially resist catalysis by phospholipase A2. However, after a latency period, they become susceptible when sufficient reaction products (lysolecithin and fatty acid) accumulate in the membrane. Temperature near the main bilayer phase transition and calcium concentration modulate the effectiveness of the reaction products. The purpose of this study was to examine the individual contributions of lysolecithin and palmitic acid to the susceptibility of dipalmitoylphosphatidylcholine vesicles and to rationalize the effects of temperature and calcium. Various fluorescent probes (Prodan, Laurdan, pyrene-labeled fatty acid, and dansyl-labeled phospholipid) were used to assess changes in the ability of the reaction products to perturb the bilayer and to affect the interactions with the enzyme. Un-ionized palmitic acid decreased bilayer polarity and perturbed the membrane surface exposing some of the Prodan to bulk water. Lysolecithin increased bilayer polarity and the rate of dipolar relaxation in response to the excited states of Laurdan and Prodan. A combination of the individual contributions of each product was observed when palmitic acid and lysolecithin were present together at low calcium, and the effects of lysolecithin dominated at high calcium. Palmitic acid, but not lysolecithin, promoted the binding of phospholipase A2 to the bilayer surface in the absence of calcium. Lysolecithin reduced the ability of fatty acid to enhance binding apparently by altering the structure of fatty acid domains in the membrane. Furthermore, increased temperature and ionization of the fatty acid tended to cause segregation of bound phospholipase A2 into domains poor in phospholipid content which presumably impeded bilayer hydrolysis. In contrast, un-ionized palmitic acid and lysolecithin promoted hydrolysis by augmenting a step distal to the adsorption of enzyme to the bilayer. This kinetic response to lysolecithin was calcium-dependent. A model accounting for these varied influences of the reaction products is presented.     

Neuropathological findings after intracerebral implantation of microdialysis catheters

The neuropathological and immunocytochemical changes in the sheep forebrain following 7 days of microdialysis, using a catheter approved for human use, are described. There was no behavioural dysfunction and light microscopy revealed mild astrogliosis and patchy macrophage infiltration immediately adjacent to the catheter track. The surrounding neuropil was normal. There was one small subcortical haemorrhage (10 x 1.5 mm). These findings are similar to those following microdialysis in rodents and suggest that the risk of significant damage to the human brain is low, that neuropathological changes in the brain around the catheter should not interfere with local brain metabolism, and that the catheter should be affixed in such a way as to minimize movement-induced damage to the brain.     

Pre-incision infiltration with lidocaine reduces pain and opioid consumption after reduction mammoplasty

BACKGROUND: The main purpose of the reconstruction of the cranium is the protection of the brain. Besides we have to consider important functional and aesthetic necessities in order to achieve satisfactory results. METHODS: Thirty-six clinical cases, operated from November 1991 to June 1996, in which the reconstruction of the cranial vault is carried out by a polymethylmethacrylate acrylic resin are analysed. The causes and locations of the most common bone defects and the main indications for reconstruction are examined. While the repair of the osseous gaps caused by neoplasms is immediate, in the traumatic occurrences, in order to reduce the probability of infectious complications, an average time of 11 months elapsed from the first operation. The surgical technique, with slightest alterations, is the same in all the presented cases, preparing the acrylic resin straight on the operating table. The resin, moulded and adapted to the defect until its complete hardening, presents, thanks to its properties, manifold advantages (and few real disadvantages). RESULTS: The results, in terms of complications, are very satisfactory, with an infectious rate of 2.7%. Besides, in one third of the patients, a considerable clinical improvement after the repair has been observed. CONCLUSIONS: According to personal experience, it is possible to affirm that polymethylmethacrylate, with its remarkable plasticity and stability in time, can always guarantee a satisfactory functional and aesthetic result.     

硫酸盐含量对全固废材料固化盐渍土抗压强度的影响

为探讨硫酸盐含量对全固废材料固化盐渍土抗压强度及微观结构的影响,采用击实试验和无侧限抗压强度试验,并结合扫描电镜、EDS、X射线衍射和热重分析等微观测试结果,从固化盐渍土的火山灰反应产物及其数量等角度分析含盐量对固化盐渍土抗压强度变化的影响。结果表明:硫酸盐含量低于2.7%时,固化盐渍土抗压强度随含盐量的增加呈先增大后减小,抗压强度峰值对应的含盐量为1.8%;固化盐渍土的火山灰反应产物主要为C-S-H和AFt,硫酸盐含量从0.3%增至1.8%时,反应产物明显增多,致使固化土抗压强度增大;但当硫酸盐含量从1.8%增至2.7%时,膨胀性AFt将试件内部孔隙完全填充并产生胀裂破坏,造成抗压强度降低。研究成果为全固废材料固化硫酸盐渍土的工程应用奠定了基础,对环境保护也有积极贡献。     

不同污泥干化焚烧技术路线全链条碳足迹分析

碳足迹分析是目前国际上常用的技术能耗评估和资源优化配置的方法.文中采用IPCC《国家温室气体清单指南》提供的方法,对干化-焚烧、深度脱水-干化-焚烧、厌氧消化-深度脱水-干化-焚烧3种基于焚烧的污泥处理处置技术路线进行碳足迹分析.结果表明,污泥干化-焚烧技术路线净碳排放量最低.厌氧消化虽然是污泥资源化利用的重要方式,但由于我国污泥有机质偏低,污泥单独厌氧产气率低,沼气利用产生的能量不足以弥补该过程的消耗.污泥干化和脱水环节产生的碳排放量较大,因此,优化热源、减少药剂使用可以实现碳减排;另一方面,推行污泥与城市有机固废高效协同厌氧,提高沼气产率,增加碳汇,也可以减少总的碳排放量.     

Melanin Distribution in Human Skin: Influence of Cytoskeletal,Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs.     

Environmental Control Symposium

MAN is but a part of the universe; his capabilities make him a significant link, in the cycle of life. To ensure this life, man must live in harmony with his environment. Recently, a disharmony has been discovered which could have grave effects upon the existence of man. It appears that man in his great thrust forward is destroying his own environment. The gravity of this threat to man's own existence carries some intrinsic problems of its own: man must allow his reason rather than his emotion to take command.