Zeolite protects mice from iron-induced damage in a mouse model trial

© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. For centuries, zeolites have been used for their utility in binding metals, and they feature in a multitude of agricultural and industrial applications in which the honeycombed zeolite structures form ideal ion exchangers, catalysts and binding agents. Zeolites are currently in a transition period, moving towards implementation in human ailments and diseases. Here, we postulated that zeolites may be able to counter the effects of excess iron and conducted a mouse model trial to gauge the utility of this notion. We used the transgenic mouse strain MexTAg299 for a thirty-week pilot trial in which iron polymaltose and/or the zeolite clinoptilolite was injected into the peritoneum twice weekly. Mice were sacrificed at the end of the trial period and examined by postmortem and histology for significant physiological differences between mouse subgroups. In this study, we demonstrated that a common zeolite, clinoptilolite, is able to maintain the general health and well-being of mice and prevent iron-induced deleterious effects following iron overload. When zeolites are given with iron biweekly as intraperitoneal injections, mice showed far less macroscopic visual organ discoloration, along with near normal histology, under iron overload conditions when compared to mice injected with iron only. The purpose of the present pilot study was to examine potential alternatives to current iron chelation treatments, and the results indicate an advantage to using zeolites in conditions of iron excess. Zeolites may have translational potential for use in cases of human iron overload

Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma.

Malignant mesothelioma (MM) is an almost invariably fatal cancer caused by asbestos exposure. The toxicity of asbestos fibers is related to their physicochemical properties and the generation of free radicals. We set up a pilot study to investigate the potential of the zeolite clinoptilolite to counteract the asbestos carcinogenesis by preventing the generation of reactive nitrogen and oxygen radicals. In cell culture experiments, clinoptilolite prevented asbestos-induced cell death, reactive oxygen species production, DNA degradation, and overexpression of genes known to be up-regulated by asbestos. In an asbestos-induced transgenic mouse model of MM, mice were injected intraperitoneal injections with blue asbestos, with or without clinoptilolite, and monitored for 30 weeks. By the end of the trial all 13 mice injected with asbestos alone had reached humane end points, whereas only 7 of 29 mice receiving crocidolite and clinoptilolite reached a similar stage of disease. Post-mortem examination revealed pinpoint mesothelioma-like tumors in affected mice, and the absence of tumor formation in surviving mice. Interestingly, the macrophage clearance system, which was largely suppressed in asbestos-treated mice, exhibited evidence of increased phagocytosis in mice treated with asbestos and clinoptilolite. Our study suggests that inhibiting the asbestos-induced generation of reactive oxygen species and stimulating the macrophage system may represent a pathway to amelioration of asbestos-induced toxicity. Additional studies are warranted to explore the underlying mechanisms responsible for our observations

Validation of simplified tying force method for robustness assessment of RC framed structures

The robustness of reinforced concrete (RC) structures is an important ongoing research topic in the civil engineering community. Especially in the last decades, the need for structural robustness assessment methods has become urgent, and several design methods have been proposed in codes and guidelines to mitigate the progressive collapse risk of reinforced concrete structures. The most used approaches are the Tying Force and Alternate Load Path methods. The first is typically applied as an indirect and prescriptive method where the building is considered mechanically tied together and able to enhance continuity and the resistance to progressive collapse. The second is a direct method, where the capacity of the structure to sustain the applied loads is evaluated after the loss of a load-bearing element, most effectively using advanced nonlinear structural analysis methods. In the context of the Tying Force method, the Eurocode is recognised to underestimate the tie force demands required by building structures subject to the loss of a load bearing member, which are better reflected in the USA UFC Guidelines. A new Tying Force method has been proposed by Izzuddin & Sio (2021) for the next generation of the Eurocodes, which addresses the shortcomings of the present Eurocode guidance, and provides a more comprehensive treatment than considered in the UFC code. The present paper is aimed specifically at the validation of the new Simplified Tying Force method (Izzuddin & Sio, 2021) for reinforced concrete structures, considering grillage and combined beam/slab floor systems, and considering the rotational ductility of such structures, which is explicitly considered in the new method

Validation of simplified tying force method for robustness assessment of RC framed structures

The robustness of reinforced concrete (RC) structures is an important ongoing research topic in the civil engineering community. Especially in the last decades, the need for structural robustness assessment methods has become urgent, and several design methods have been proposed in codes and guidelines to mitigate the progressive collapse risk of reinforced concrete structures. The most used approaches are the Tying Force and Alternate Load Path methods. The first is typically applied as an indirect and prescriptive method where the building is considered mechanically tied together and able to enhance continuity and the resistance to progressive collapse. The second is a direct method, where the capacity of the structure to sustain the applied loads is evaluated after the loss of a load-bearing element, most effectively using advanced nonlinear structural analysis methods. In the context of the Tying Force method, the Eurocode is recognised to underestimate the tie force demands required by building structures subject to the loss of a load bearing member, which are better reflected in the USA UFC Guidelines. A new Tying Force method has been proposed by Izzuddin & Sio (2021) for the next generation of the Eurocodes, which addresses the shortcomings of the present Eurocode guidance, and provides a more comprehensive treatment than considered in the UFC code. The present paper is aimed specifically at the validation of the new Simplified Tying Force method (Izzuddin & Sio, 2021) for reinforced concrete structures, considering grillage and combined beam/slab floor systems, and considering the rotational ductility of such structures, which is explicitly considered in the new method