Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Advances in bioglass and glass ceramics for biomedical applications

© Springer-Verlag GmbH Germany 2017. Tissue engineering and advanced biomedical technologies have proved to be potential to improve the quality of human life. During the last four decades, the capability to engineer or repair new functional tissues has been a very effective approach to improve the quality of life of patients. Since its discovery by Hench and co-workers in the 1960s, bioglasses and glass ceramics have attracted considerable attention of many researchers because of their unique properties which can easily be tailored by manipulating its compositions and morphology. Over the years, many questions concerning its interactions with both hard and soft tissues have been answered with a multidisciplinary team of surgeons, scientists and engineers. Many clinical Bioglass® and other similar structures and compositions are being used for bone augmentation and restoration, in orthopaedic, dental and maxillofacial surgery and in general in the field of tissue engineering. They have proved to be efficient and effective, some with outperformance over other bioceramic and metal prostheses. It is our aim in this chapter to present the development of these important biomaterials focusing on the history, synthesis, properties, modern characterisation methods and the current development of nano- and biocomposite materials for clinical applications

The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts

Establishing and maintaining mature bone at the bone-device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti-6Al-4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti-6Al-4V surfaces. Western blotting demonstrated that modifying Ti-6Al-4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti-6Al-4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue-device interface. © 2005 Elsevier Ltd. All rights reserved