The role of mitochondrial function and metabolism

"Optimal organismal function and survival in adverse conditions require robust homeostatic responses to challenging environmental conditions. Surviving a severe infection requires the synergy between resistance and disease tolerance, two evolutionarily conserved defense strategies that limit disease severity. Sepsis – a dysregulated host response to infection that leads to high risk of death – is a prime example of extreme homeostasis disruption and therefore constitutes an excellent model to study homeostasis and inter-organ communication principles.(...)

Anti-inflammatory and antinociceptive activities of indole–imidazolidine derivatives

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs) represent a group of approximately 50 different medicines that are widely prescribed for the management of inflammation and that exhibit variable anti-inflammatory, anti-pyretic and analgesic activities. Most NSAIDs also exhibit a shared set of adverse effects, particularly related to gastrointestinal complications; thus, the development of new drugs for the treatment of chronic inflammation and pain continues to be an issue of high interest. Hydantoin and indole derivatives are reported to possess various pharmacological effects, including anti-inflammatory and analgesic activities. Therefore, the aim of this study was to evaluate the potential anti-inflammatory and antinociceptive activities of hybrid molecules containing imidazole and indole nuclei. The anti-inflammatory activities of 5-(1H-Indol-3-yl-methylene)-2-thioxo-imidazolidin-4-one (LPSF/NN-56) and 3-(4-Bromo-benzyl)-5-(1H-indol-3-yl-methylene)-2thioxo-imidazolidin-4-one (LPSF/NN-52) were evaluated using air pouch and carrageenan-induced peritonitis models as well as an acetic acid-induced vascular permeability model followed by IL-1β and TNF-α quantification. To evaluate the antinociceptive activities of the compounds, acetic acid-induced nociception, formalin and hot plate tests were also performed. The anti-inflammatory activities of the compounds were evidenced by a reduction in both leukocyte migration and the release of TNF-α and IL-1β in air pouch and peritonitis models. Upon acetic acid-induced nociception, a decrease in the level of abdominal writhing in the groups treated with LPSF/NN-52 (52.1%) or LPSF/NN-56 (63.1%) was observed. However, in the hot plate test, none of the derivatives tested exhibited an inhibition of nociception. These results indicate that the compounds tested exhibited promising anti-inflammatory and antinociceptive activities that likely involved the modulation of the immune system

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved