Characterization, reactivity and rheological behaviour of metakaolin and Meta-halloysite based geopolymer binders

The type of aluminosilicate precursor used in the synthesis of geopolymer binders plays a huge role in the resulting performance. Thus, it is critical to understand the properties of precursors and how they influence the corresponding performance of geopolymer binders. In this study, metakaolin and meta halloysite are used as the aluminosilicate precursor in the synthesis of geopolymer binders. These precursors are obtained locally in order to propel the sustainable development and application of geopolymers. The precursors were characterized and the corresponding influence on the reactivity, rheology and setting times of geopolymers was investigated. In addition to the influence of precursor type on the properties of the geopolymers, the effect of two silica moduli (i.e. 1.3 and 1.5) was also evaluated. The results from this study indicated that increasing the activator silica modulus from 1.3 to 1.5 extended the setting times and increased the stress strain of the geopolymer binders. Characterization of the precursors indicated that metakaolin has a higher amorphous content compared to that of meta halloysite. However, the finer particles of meta halloysite embodied it with the ability to participate in a faster geopolymerization and result in more formation of activation products

NADPH:cytochrome c (P450) reductase activates tirapazamine (SR4233) to restore hypoxic and oxic cytotoxicity in an aerobic resistant derivative of the A549 lung cancer cell line

Tirapazamine (TPZ, SR4233, WIN 59075) is a bioreductive drug that is activated in regions of low oxygen tension to a cytotoxic radical intermediate. This labile metabolite shows high selective toxicity towards hypoxic cells, such as those found in solid tumours. Under aerobic conditions, redox cycling occurs with subsequent generation of superoxide radicals, which are also cytotoxic. NADPH:cytochrome c (P450) reductase (P450R) is a one-electron reducing enzyme that efficiently activates TPZ. Recently a derivative of the A549 non-small cell lung cancer cell line (A549c50) was generated that showed substantially reduced P450R activity compared to its parental line (Elwell et al (1997) Biochem Pharmacol54: 249–257). Here, it is demonstrated that the A549c50 cells are markedly more resistant to TPZ under both aerobic and hypoxic conditions. In addition, these cells have a dramatically impaired ability to metabolize TPZ to its two-electron reduction product, SR4317, under hypoxic conditions when compared to wild-type cells. P450R activity in the A549c50 cells was reintroduced to similar levels as that seen in the parental A549 cells by transfection of the full-length cDNA for human P450R. These P450R over-expressing cells exhibit restored sensitivity to TPZ under both aerobic and hypoxic conditions, comparable to that found in the original parental A549 cells. Further, the ability of the transfected cells to metabolize TPZ to SR4317 under hypoxic conditions is also shown to be restored. This provides further evidence that P450R can play an important role in the activation, metabolism and toxicity of this lead bioreductive drug. © 2000 Cancer Research Campaig

17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

The putative oestrogen receptor negative human breast cancer cell line MDA231, when grown as tumours in mice continually receiving 17β-oestradiol, showed substantially increased growth rate when compared to control animals. Further, we observed that 17β-oestradiol treatment could both increase the growth rate of established MDA231 tumours as well as decreasing the time taken for initiating tumour growth. We have also demonstrated that this increase in growth rate is accompanied by a four-fold increase in nitric oxide synthase activity, which was predominantly the inducible form. Inducible-nitric oxide synthase expression in these tumours was confirmed by immunohistochemical analysis and appeared localized primarily in areas between viable and necrotic regions of the tumour (an area that is presumably hypoxic). Prophylactic treatment with the nitric oxide synthase inhibitor nitro-L-arginine methyl ester resulted in significant reduction in this apparent 17β-oestradiol-mediated growth promoting effect. Tumours derived from mice receiving 17β-oestradiol-treatment were characterized by a significantly lower fraction of perfused blood vessels and an indication of an increased hypoxic fraction. Consistent with these observations, 17β-oestradiol-treated tumours were less radio-responsive compared to control tumours when treated with a single radiation dose of 15 Gy. Our data suggests that long-term treatment with oestrogen could significantly alter the tumour oxygenation status during breast tumour progression, thus affecting response to radiotherapy

The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines

Clinical usefulness of doxorubicin (DOX) is limited by the occurrence of multidrug resistance (MDR) associated with the presence of membrane transporters (e.g. P-glycoprotein, MRP1) responsible for the active efflux of drugs out of resistant cells. Doxorubicin is a well-known bioreductive antitumour drug. Its ability to undergo a one-electron reduction by cellular oxidoreductases is related to the formation of an unstable semiquionone radical and followed by the production of reactive oxygen species. There is an increasing body of evidence that the activation of bioreductive drugs could result in the alkylation or crosslinking binding of DNA and lead to the significant increase in the cytotoxic activity against tumour cells. The aim of this study was to examine the role of reductive activation of DOX by the human liver NADPH cytochrome P450 reductase (CPR) in increasing its cytotoxic activity especially in regard to MDR tumour cells. It has been evidenced that, upon CPR catalysis, DOX underwent only the redox cycling (at low NADPH concentration) or a multistage chemical transformation (at high NADPH concentration). It was also found, using superoxide dismutase (SOD), that the first stage undergoing reductive activation according to the mechanism of the redox cycling had the key importance for the metabolic conversion of DOX. In the second part of this work, the ability of DOX to inhibit the growth of human promyelocytic-sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX) was studied in the presence of exogenously added CPR. Our assays showed that the presence of CPR catalysing only the redox cycling of DOX had no effect in increasing its cytotoxicity against sensitive and MDR tumour cells. In contrast, an important increase in cytotoxic activity of DOX after its reductive conversion by CPR was observed against HL60 as well as HL60/VINC and HL60/DOX cells

Polysialate matrixes from Al-rich and Si-rich metakaolins: Polycondensation and physico-chemical properties

Two metakaolins from Al-rich and Si-rich kaolinitic clays were used to design polysialate matrices with different Si/Al and NaK/Al ratios. The aim was to investigate the influence of oligomers formed during dissolution and hydrolysis on the polycondensation and transformation to hard and stable matrices. Products of geopolymerization of the different matrices were subjected to mechanical testing considering various loading configurations. The geopolymer matrices showed compressive strength from 51 ± 5 MPa (Si/Al=1.23) to 61 ± 2 MPa (Si/Al = 2.42) and bi-axial four-point strength from 11 ± 2 MPa to 16 ± 1.1 MPa respectively. These results were consistent with density, leaching ability and microstructure. It is proposed that the mechanical properties and the stability of the products of reactions can be discussed as the important parameters for the evaluation of the quality of geopolymer matrices. Moreover, polycondensation and the final performance of the product are greatly influenced by the unreacted crystalline or semi-crystalline phases that act as fillers and contribute to increased stability and mechanical properties. A good geopolymer material resulting from our study will be defined as an amorphous matrix of polysialates in which various unreacted or partly reacted crystalline phases are embedded. It is suggested that Si-rich metakaolin will present the more hardening and stable matrix with shorter setting time leading to small pores and an enhanced interlocked microstructure

Cleaner production of the lightweight insulating composites: Microstructure, pore network and thermal conductivity

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