Aune Rehema

The Swedish APP670/671 Alzheimer’s Disease Mutation: The First Evidence for Strikingly Increased Oxidative Injury in the Temporal Inferior Cortex

To evaluate the level of oxidative stress (OS) in familial Alzheimer’s disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid peroxides and protein carbonyls, compared to sporadic Alzheimer’s disease (AD). Compared with TIC from sporadic AD patients, the mutation carriers showed a markedly decreased activity of catalase (CAT) in the same area, and the same trend was found for another antioxidant enzyme, superoxide dismutase. These results are consistent with the deep oxidative injury of TIC in Swedish FAD. In the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative injury tended to be higher than in sporadic AD. Only the increase in the levels of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant. Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.

Complete glutathione system in probiotic Lactobacillus fermentum ME-3

There is much information about glutathione (GSH) in eukaryotic cells, but relatively little is known about GSH in prokaryotes. Without GSH and glutathione redox cycle lactic acid bacteria (LAB) cannot protect themselves against reactive oxygen species. Previously we have shown the presence of GSH in Lactobacillus fermentum ME-3 (DSM14241). Results of this study show that probiotic L. fermentum ME-3 contains both glutathione peroxidase and glutathione reductase. We also present that L. fermentum ME-3 can transport GSH from environment and synthesize GSH. This means that it is characterized by a complete glutathione system: synthesis, uptake and redox turnover ability that makes L. fermentum ME-3 a perfect protector against oxidative stress. To our best knowledge studies on existence of the complete glutathione system in probiotic LAB strains are still absent and glutathione synthesis in them has not been demonstrated.

Could long-term alimentary iron overload have an impact on the parameters of oxidative stress? A study on the basis of a village in southern Estonia.

The effects of long-term alimentary (drinking water) iron overload on the parameters of oxidative stress were evaluated. The study group (n = 35) from a village in southern Estonia was 37.1 ± 13.3 years old, and the mean period of drinking water iron overload was 20.6 ± 9.3 years. The serum iron content was significantly higher than normal. The total iron-binding capacity of serum tended to be lowered. There was no change in the transferrin content. The parameters of lipid peroxidation like conjugated dienes and thiobarbituric acid reactive substances showed also significant differences. In addition, the red blood cell glutathione content was also decreased. The total antioxidant capacity of serum was not changed. It can be concluded from our results that a long-term alimentary iron overload results in a positive serum iron balance, which, in turn, yields an increased oxidative stress.

An antioxidant probiotic reduces postprandial lipemia and oxidative stress

Reducing postprandial oxidative stress (OxS), decreasing postprandial blood triglyceride level (TG) and improving lipoprotein status is likely to have a preventive impact on the development of cardiovascular disease (CVD). Previously we have shown that the antioxidant probiotic Lactobacillus fermentum ME-3 (DSM14241) is characterized by antiatherogenic effects. This randomized double-blind placebo-controlled study evaluated the influence of kefir enriched with an antioxidative probiotic L. fermentum ME-3 (LfKef) on postprandial OxS, blood TG response and lipoprotein status. 100 clinically healthy subjects were recruited into the study. Blood parameters of postprandial OxS, TG and lipoprotein status were determined by oxidized LDL, baseline diene conjugation in LDL (BDC-LDL), oxidized LDL complex with beta-2 glycoprotein (Beta2-GPI-oxLDL), paraoxonase (PON) activity, LDL-Chol, HDL-Chol and TG. To evaluate general body postprandial OxS-load we measured 8-isoprostanes (8-EPI) in the urine. Consumption of LfKef significantly reduced the postprandial level of oxidized LDL, BDC-LDL, Beta2-GPI-oxLDL, urinary 8-isoprostanes and postprandial TG and caused a significant increase in HDL-Chol and PON activity. This is the first evidence that kefir enriched with an antioxidant probiotic may have a positive effect on both postprandial OxS and TG response as well as on lipoprotein status.

Successful management of mild atopic dermatitis in adults with probiotics and emollients

Atopic dermatitis is characterized by impaired skin and mucous membrane barrier function. Measures improving barrier integrity decrease the influence of environmental factors that might exacerbate inflammation. Ten adult patients with mild-to-moderate atopic dermatitis consumed for three months fermented with potent antioxidative probiotic, L. fermentum ME-3 (DSM 14241) goat milk 200 mg/day. A control group consisted of six patients, not supplemented by probiotic. All patients used emollients regularly. Skin iron levels, glutathione redox ratios (GSSG/GSH), diene conjugate (DC) amounts, blood glutathione status, oxidized low-density lipoprotein (oxLDL), and total antioxidativity was measured at the baseline and after three months. A significant decrease in skin iron levels, DC amounts, and glutathione redox ratio occurred in the probiotic-supplemented group compared to the control group (P < 0.05 for all indices). In the same group, blood levels of oxLDL decreased (p < 0.05), and GSH levels increased (P < 0.001) with concomitant improvement in the GSSG/GSH ratio. Blood antioxidativity markers also showed an improvement. The results of our study demonstrate that regular use of probiotics with antioxidative properties coupled with the use of lipid-containing emollients considerably decreases inflammation and concomitant oxidative stress in adult patients with mild-to-moderate atopic dermatitis. This effect was observed both in the skin and in the blood.

Nickel sulphate and epoxy resin: differences in iron status and glutathione redox ratio at the time of patch testing

The reactive patch test reaction is a useful model to characterize oxidative stress in acute allergic contact dermatitis. This model was used to study oxidative stress in the skin of individuals allergic to nickel and epoxy resin. The study included six and five patients, respectively, whose skin was simultaneously biopsied from a positive patch test site and from an apparently healthy area. The biopsies were homogenized and used for determination of iron content, unbound iron binding capacity, diene conjugate levels, and glutathione redox ratio. A positive test reaction to 5% nickel sulphate was accompanied by 2.5-fold increase in iron level as compared to apparently healthy skin (P<0.1). The percentage saturation of iron-binding capacity and the glutathione redox ratio were significantly increased (P<0.01 and P<0.05, respectively). Reactive patch test responses to 1% epoxy resin were not accompanied by clear alterations in iron status or glutathione redox ratio. Our investigation showed that apart from oxidative burst caused by accumulation of inflammatory cells, hapten properties might also influence the oxidative stress status of the skin. The high incidence of nickel allergy may be attributed, at least in part, to the influence of nickel ions on the glutathione redox ratio and iron status of the skin.

Proteomic proof that a probiotic elevatesglutathione level in human serum

Abstract Lactobacillus fermentum ME-3 (LfME-3) has been proven to synthesize and secrete glutathione. A regular use of the foods fermented by it has shown a favourable influence on human lipid profiles and several antioxidant parameters. We administered the LfME-3-fermented kefir for 14 days to 43 human subjects and evaluated their serum with MALDI-TOF mass spectrometer at the beginning and end of the test period. We found an increase of the peak at m/z 308 (corresponding to glutathione) and a new peak at m/z 1467.

Emollient cream and topical glucocorticoid treatment of chronic hand dermatitis: influence on oxidative stress status of the skin

To the Editor Exacerbation of skin inflammation is accompanied by excessive production of reactive oxygen species (ROS) like superoxide (O2 + ) and hydroxyl radical (OH+) [1]. Besides damaging lipids, proteins and nucleic acids [2], some of ROS (e.g. superoxide anion) are capable of reducing transition metal ions, releasing iron from storage proteins, e.g. ferritin [1]. Excess of ‘free’ iron amplifies the formation of free radicals, especially those involved in lipid peroxidation (LP) [3]. Inside the cells, ROS are detoxified primarily by reduced glutathione (GSH) [4]. Removal of peroxides by this antioxidant results in generation of oxidized glutathione (GSSG) [5]. Therefore, the cellular redox status is best characterized by the glutathione redox ratio (GSSG/GSH). The aim of our study was to determine how different treatment regimes influence the iron status, diene conjugate amount, and glutathione redox ratio in lesional skin of patients with exacerbated chronic hand dermatitis. The study, approved by the local ethics committee, included twelve patients (11 women and a man, aged 21 /63). Skin punch biopsies of 4 mm were obtained from involved hand skin and apparently healthy skin from the back prior to the study, and an additional biopsy was obtained from treated hand skin. Four healthy subjects’ skin (a man, and three women, aged 22 /35) was also biopsied for comparison of skin iron levels. One six-patient group was treated with Locobase† REPAIR cream 4 /6 times/day, another with Fucicort cream (betamethasonum 0.1%, acidum fusidicum 2%) twice a day in combination with the emollient Locobase† fatty cream 4 /6 times/day. The treatment period lasted from 6 to 10 weeks until improvement. Biopsies were homogenized and used for assays. For determination of iron content and unsaturated iron binding capacity (UIBC) the Sigma 565 kit was used [6]. Total iron binding capacity (TIBC) was calculated as the sum of iron and UIBC values. The level of diene conjugates (DC) was determined as previously described [7]. Glutathione was measured by the method described earlier [8]. The glutathione redox ratio was expressed as GSSG/ GSH. Before treatment, the iron level in lesional skin of all 12 patients as compared to apparently healthy skin (5859/736 and 4059/446 mM/g skin, respectively) was non-significantly, DC level significantly (6609/282 and 3349/174 mM/g skin, P / 0.002), and GSSG/GSH also significantly (0.409/ 0.19 and 0.189/0.11, P /0.002) increased. UIBC and TIBC values did not differ. After therapy, glutathione redox ratio decreased significantly (P /0.0002) while iron and DC levels in lesional skin remained high as compared to clinically undamaged skin. The patients’ normal skin demonstrated approximately 2.5 times higher iron concentration than healthy individuals’ skin. As shown in Fig. 1, both selected treatment regimes equally improved the GSSG/GSH ratio but neither of them affected the iron level. Although our investigation included a limited number of patients, we can assume that more intensive LP in the lesions of chronic hand dermatitis is due to ‘free’ iron as in patients’ skin the iron level was 2.5 times higher than in healthy control subjects. Furthermore, the iron level in normal skin was significantly associated with disease duration. Redox active iron could trigger additional LP. Skin barrier function is intimately associated with lipid metabolism. Intensive LP, besides damaging cell membranes may affect skin barrier lipids [9] that might lead to further damage of the skin barrier function. Glutathione has been postulated to play an important role in inhibiting contact dermatitis [4]. Increase of GSSG/GSH before treatment and decrease after it confirms direct connection beJournal of Dermatological Science (2003) 33, 127 /129

Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study

Purpose The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. Methods This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. Results After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. Conclusions The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.