The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid

Mild cerebellar injury does not significantly affect cerebral white matter microstructural organization and neurodevelopmental outcome in a contemporary cohort of preterm infants

BackgroundPreterm birth is associated with an increased risk of cerebellar injury. The aim of this study was to assess the impact of cerebellar hemorrhages (CBH) on cerebral white matter microstructural tissue organization and cerebellar volume at term-equivalent age (TEA) in extremely preterm infants. Furthermore, we aimed to evaluate the association between CBH and neurodevelopmental outcome in late infancy.MethodsA total of 24 preterm infants with punctate CBH were included and each matched to two preterm control infants. T1-, T2-weighted images and diffusion-weighted imaging were acquired on a 3T magnetic resonance imaging (MRI) system. Regions of interest were drawn on a population-specific neonatal template and automatically registered to individual fractional anisotropy (FA) maps. Brain volumes were automatically computed. Neurodevelopmental outcome was assessed using the Bayley scales of Infant and Toddler Development at 2 years of corrected age.ResultsCBHs were not significantly related to FA in the posterior limb of the internal capsule and corpus callosum or to cerebellar volume. Infants with CBH did not have poorer neurodevelopmental outcome compared with control infants.ConclusionThese findings suggest that the impact of mild CBH on early macroscale brain development may be limited. Future studies are needed to assess the effects of CBH on long-Term neurodevelopment

Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions

Only about one third of humans possess a microbiota capable of transforming the dietary isoflavone daidzein into equol. Little is known about the dietary and physiological factors determining this ecological feature. In this study, the in vitro metabolism of daidzein by faecal samples from four human individuals was investigated. One culture produced the metabolites dihydrodaidzein and O-desmethylangolensin, another produced dihydrodaidzein and equol. From the latter, a stable and transferable mixed culture transforming daidzein into equol was obtained. Molecular fingerprinting analysis (denaturing gradient gel electrophoresis) showed the presence of four bacterial species of which only the first three strains could be brought into pure culture. These strains were identified as Lactobacillus mucosae EPI2, Enterococcus faecium EPI1 and Finegoldia magna EPI3, and did not produce equol in pure culture. The fourth species was tentatively identified as Veillonella sp strain EP. It was found that hydrogen gas in particular, but also butyrate and propionate, which are all colonic fermentation products from poorly digestible carbohydrates, stimulated equol production by the mixed culture. However, when fructo-oligosaccharides were added, equol production was inhibited. Furthermore, the equol-producing capacity of the isolated culture was maintained upon its addition to a faecal culture originating from a non-equol-producing individual