DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

The accuracy of methods for urate crystal detection in synovial fluid and the effect of sample handling: A systematic review

This study aims to compare different methods of monosodium urate crystal (MSU) detection in synovial fluid (SF) and the effect of sample storage and handling on crystal detection. A systematic literature search was performed in MEDLINE, EMBASE, the Cochrane Library and the American College of Rheumatology/European League Against Rheumatism conference abstracts of 2010 and 2011. Studies that compared a method for detecting MSU crystals in SF with polarised light microscopy (PLM) or compared various SF storage and handling factors with the detection of MSU crystals as an outcome were included. Twelve studies out of 247 identified references were included in the review. Seven studies compared different methods of MSU crystal detection in SF with PLM. Due to study heterogeneity, methodological limitations and risk of bias, no firm conclusions could be drawn from the available data. Five studies examining SF storage and handling factors were identified. A reduction in MSU crystal concentration was observed over time at room temperature that was not seen in refrigerated samples. The use of anticoagulation as a storage medium provided no benefit. Dried cytospin preparations appeared to be a suitable medium for long-term storage and delayed crystal analysis for at least 12 months. The existing data do not provide a compelling argument for the replacement of PLM as the current standard. SF sample storage and handling have an effect on MSU crystals and may impact on the reliability of analysis.S. W. Graf, R. Buchbinder, J. Zochling, S. L. Whittl

Glucosinolates in Brassica foods: bioavailability in food and significance for human health

Glucosinolates are sulphur compounds that are prevalent in Brassica genus. This includes crops cultivated as vegetables, spices and sources of oil. Since 1970s glucosinolates and their breakdown products, have been widely studied by their beneficial and prejudicial biological effects on human and animal nutrition. They have also been found to be partly responsible for the characteristic flavor of Brassica vegetables. In recent years, considerable attention has been paid to cancer prevention by means of natural products. The cancer-protective properties of Brassica intake are mediated through glucosinolates. Isothyocianate and indole products formed from glucosinolates may regulate cancer cell development by regulating target enzymes, controlling apoptosis and blocking the cell cycle. Nevertheless, variation in content of both glucosinolates and their bioactive hydrolysis products depends on both genetics and the environment, including crop management practices, harvest and storage, processing and meal preparation. Here, we review the significance of glucosinolates as source of bioactive isothiocyanates for human nutrition and health and the influence of environmental conditions and processing mechanisms on the content of glucosinolate concentration in Brassica vegetables. Currently, this area is only partially understood. Further research is needed to understand the mechanisms by which the environment and processing affect glucosinolates content of Brassica vegetables. This will allow us to know the genetic control of these variables, what will result in the development of high quality Brassica products with a health-promoting activity.Peer reviewe