Activation of coagulation and platelets by candidate membranes of implantable devices in a whole blood model without soluble anticoagulant.

Implantable devices are challenged with thrombus formation at their biomaterial interface. Thus the importance of identifying compatible biomaterials that will help to improve the performance of these devices are becoming increasingly paramount. The aim of this study was to evaluate the activation of coagulation and platelets by candidate membranes considered for use in implantable devices on the basis of an adapted whole blood model without soluble anticoagulants. Evaluated materials were incubated with whole blood without soluble anticoagulant in wells coated with heparin. Prothrombin fragment 1+2 (PTF 1+2), thrombin-antithrombin complex (TAT), and ß-thromboglobulin (BTG) were analyzed in plasma samples using enzyme immunoassays. The C5 inhibitor eculizumab was used to evaluate the role of complement. Incubation of two of the polyamide membranes PAR and PATF led to an increase in concentration of PTF 1+2 and TAT (p < 0.01 for PAR, ns for PATF). The BTG concentration was significantly increased for five materials [PAR, PATF, polycarbonate (PC), and two polyarylethersulphone membranes PAES-1 and PAES-2]. Complement inhibition had no effect on coagulation or platelet activation induced by PAR and PATF. In conclusion, PAR and PATF were not compatible with blood and should be avoided for use in implantable devices.

Inflammatory response induced by candidate biomaterials of an implantable microfabricated sensor.

The implantation of synthetic medical devices is known to generate an immediate and complex material-related inflammatory response. Consequently, 15 candidate materials for a new microfabricated sensor were investigated. A human whole blood model that permits the interaction of all the putative inflammatory systems was used. The experiments were performed by administering 500 µL of lepirudin-anticoagulated blood in each well of a 24-well polystyrene microtiter plate preloaded with the respective materials. The degree of inflammation was evaluated by assessing four complement activation markers, six proinflammatory cytokines, and chemokines, the expression of monocyte tissue factor (TF), as well as platelet activation. The complement system was inhibited with the C5-inhibitor eculizumab. Three of the materials distinctly activated complement through the alternative pathway, whereas the rest of the materials were virtually inert. Notably, the same three materials induced a marked and selective expression of TF as well as the release of five of the six cytokines. All these increases were statistically significant (p < 0.05). Inhibition of complement by the C5-inhibitor virtually abolished TF expression and markedly reduced several of the cytokines, suggesting that complement is a particularly useful tool to reveal the immediate inflammatory-inducing properties of these biomaterials.

Coexpression of c-erbB 1-4 receptor proteins in human glioblastomas. An immunohistochemical study.

Studies support involvement of the erbB/HER (human epidermal growth factor receptor) family, comprising the c-erbB-1/2/3/4 receptor proteins, in the tumourigenesis of human gliomas, raising their potential role in diagnostic and therapeutic approaches to these tumours. Reliable detection systems for these molecules in glioma tissue are therefore needed. Formalin-fixed and paraffin-embedded sections from twenty-one human glioblastomas were investigated by standard immunohistochemical procedures for expression of c-erbB-1/2/3/4 receptor proteins using commercial antibodies. All the antibodies used worked satisfactorily on paraffin-sections. For EGFR (epidermal growth factor receptor) two antibodies reactive against the external and internal domain were used. The first revealed positive immunoreactivity in 13 of 21 tumours (62 %), whereas all were positive with the latter. All glioblastomas were negative for the mutated variant of EGFR (i.e. EGFRvIII). Nine of 21 tumours (43 %) were immunoreactive for c-erbB-2, 19 of 20 tumours (95 %) for c-erbB-3, and 21 of 21 for c-erbB-4. Kaplan-Meier plots as a function of growth factor receptor expression did not show any significant association with survival among the glioblastoma patients. In conclusion, immunohistochemistry is well suited for detection of erb receptor proteins in glioblastoma tissue and demonstrated abundant and simultaneous immunoreactivity of these receptors.

Interface film resistivities for heat and mass transfers-integral relations verified by non-equilibrium molecular dynamics.

Integral relations that predict interface film transfer coefficients for evaporation and condensation have recently been derived. According to these relations, all coefficients can be calculated for one-component systems, using the thermal resistivity and the enthalpy profile through the interface. The integral relations were tested in this work using nonequilibrium molecular dynamics simulations for argon-like particles and n-octane molecules. The simulations confirm the integral relations within the accuracy of the calculation for both systems. Evidence is presented for the existence of an excess thermal resistivity on the gas side of the surface, and the fact that this property is decisive for interface heat and mass transfer coefficients. The integral relations were used to predict the mass transfer coefficient for n- octane as a function of surface tension. The findings are important for modeling of one-component phase transitions.

Comparison of light microscopy, in situ hybridization and polymerase chain reaction for detection of human papillomavirus in histological tissue of cervical intraepithelial neoplasia.

The aims of the study were to estimate the prevalence of HPV infection in patients treated for high grade lesions of the cervix uteri (HG CIN), and to evaluate the validity of the histological criteria used for detection of HPV infection. The study comprised 203 women treated for HG CIN by laser conization. Forty-three preoperative biopsies and 160 cone specimens were examined for HPV infection using light microscopy (LM), in situ hybridization (ISH), and polymerase chain reaction (PCR). ISH was performed using commercial biotinylated probes for HPV types 6/11, 16/18, and 31/33/35 (Vira-Type In Situ Kits, Digene Diagnostics, Silver Spring, MD). HPV-PCR was performed with the L1 consensus primers Gp5+/6+. The prevalence of HPV detected by LM was 70%; by ISH 48% and by PCR 83%. Using PCR as the gold standard, LM had a sensitivity of 0.71 and specificity of 0.41. The corresponding results for ISH were 0.51 and 0.65, respectively. The positive predictive value for both tests reached over 80%, but the negative predictive value was less than 25%. This study demonstrates that morphology is an unspecific method of identifying HPV infections. LM identification of HPV infections has no clinical implications. Our analyses comparing test performances of LM, ISH and PCR show that PCR is the superior method.