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Veiko Vengerfeldt,1 Reet Mändar,2,3 Mare Saag,1 Anneli Piir,2 Tiiu Kullisaar2 1Institute of Dental Sciences, Faculty of Medicine, University of Tartu, 2Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, 3Competence Centre on Health Technologies, Tartu, Estonia Background: Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful.Purpose: To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects.Patients and methods: The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to −80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. Results: The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p

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.

Abstract Background The aim of the study was to detect whether in experimental Salmonella enterica Typhimurium infection the probiotic Lactobacillus fermentum ME-3 in combination with fluoroquinolone therapy would eradicate S. Typhimurium, prevent the development of liver and spleen granulomas and improve the indices of oxidative stress in the ileum mucosa. The selected bacteriological, histological and biochemical methods were applied. Results Combined treatment with L. fermentum ME-3 and ofloxacin eradicated Salmonella Typhimurium from blood, ileum and liver, decreased the number of animals with liver and spleen granulomas and reduced the value of lipid peroxides in the ileum mucosa. Higher total counts of intestinal lactobacilli in all experimental groups were associated with the absence of liver granulomas. Conclusion The antimicrobial and antioxidative probiotic L. fermentum ME-3 combined with ofloxacin enhances the eradication of experimental S. Typhimurium infection. These observations on probiotic and antimicrobial co-action may serve as basis to develop new strategies for treatment of invasive bacterial infections of the gut.

Abstract Background In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. Methods Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. Results ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. Conclusion The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by improvement of some measurable laboratory indices of well-established physiological functions of host, e.g. markers of antioxidative defence system.

Background: Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients. Abdominal obesity is frequently accompanied by metabolic syndrome (MS). Adipokines are cell signaling proteins that have direct impact upon the metabolic homeostasis. The purpose of this analysis was to evaluate the effect of bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB) on the adipokine levels and metabolic profile as well as MS and status of type 2 diabetes (T2D)., Methods: We analyzed anthropometric parameters, blood levels of adipokines, vitamins, lipids and inflammatory markers in 30 bariatric surgery patients with obesity of class II or III 1 month before and 1 year after surgery as well as in 60 obese patients from general practice (GP) and 15 patients with normal body mass (control)., Results: The BMI was significantly higher among patients before surgery and GP patients in comparison to control and post-surgery patients. The levels of glucose, cholesterol and LDL-cholesterol, triglyceride and hs-CRP were the highest in patients before surgery but decreased significantly after surgery, while the level of HDL-cholesterol increased after surgery. The levels of adiponectin increased and that of leptin decreased after surgery. The significant difference in the concentration of resistin was revealed between LSG and LRYGB methods. The relationship between resistin and vitamin D was also found. The patients with MS and T2D displayed significantly greater reduction in lipid markers and adipokine levels than the rest of patients., Conclusion: Remarkable changes in levels of adipokines after bariatric surgery appear like increase in adiponectin and decrease in leptin levels. Significant improvement in anthropometric parameters, metabolic and inflammatory markers occurs, suggesting high potential for reduction of metabolic syndrome and risk for type 2 diabetes. We have shown for the first time ever that level of vitamin D may be involved in resistin regulation., (© 2022. The Author(s).)

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.

Background: Cardiovascular diseases continue to be a challenge and burden to heath. The incidence of type 2 diabetes is increasing. Modifying the (common) risk factors of them is the key of longterm success. The aim of the study was to establish if the special composition of innovative food supplement Reg'Activ Cholesterol (RAC) has a positive influence to the human body cardiovascular-inflammatory and diabetic parameters., Methods: Forty-five clinically asymptomatic participants consumed an RAC containing an antioxidative and antiatherogenic probiotic Lactobacillus fermentum ME-3 (LFME-3) for 4 weeks. The parameters measured were total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, oxLDL, hsCRP, IL-6 and glycosylated haemoglobin (HbA1c%)., Results: The cardiovascular and diabetes risk profile of the participants improved significantly after 4 weeks of the intervention. The reduction of total cholesterol (from 6.5 ± 1.0 to 5.7 ± 0.9 mmol/l, p = 9.90806E-11) was on the account of LDL cholesterol as the HDL cholesterol level rose from 1.60 ± 0.31to 1.67 ± 0.34mml/l, p = 0.01. HbA1c% was reduced from 5.85 ± 0.28 to 5.66 ± 0.25 p = 4.64E-05 and oxLDL decreased from 84 ± 20 to 71 ± 15 U/l, p = 4.66292E-08., Conclusions: The consumption of RAC in clinically asymptomatic volunteers with borderline-high values of risk factors for cardiovascular disease (BMI, HbA1c%, LDL cholesterol) for 4 weeks had a positive effect on blood lipoprotein, oxidative stress and inflammatory profile. There are no human trials published before with RAC., Trial Registration: The trial described here isa n open label pilot study within the framework of a larger special clinical trial ( ISRCTN55339917 ) [Accessed 20 Feb 2016].

In this study, we aimed to compare the level of zinc, selenium, glutathione peroxidase activity and antioxidant status in following populations of men: severe inflammation in prostate (>10(6) white blood cells in prostate secretion; n=29), severe leukocytospermia, (>10(6) white blood cells in semen; n=31), mild inflammation, (0.2-1M white blood cells in semen or prostate secretion; n=24), non-inflammatory oligozoospermia (n=32) and healthy controls (n=27). Male partners of infertile couples had reduced level of antioxidative activity, selenium and zinc in their seminal plasma. Most importantly, reduced selenium levels were evident in all patient groups regardless of inflammation status. Therefore, these patients might gain some benefit from selenium supplementation., (Copyright © 2014. Published by Elsevier GmbH.)

The male factor accounts for almost 50% of infertility cases. Inflammation may reduce semen quality via several pathways, including oxidative stress (OxS). As male infertility routinely is assessed using semen analysis only, the possible presence of non-leukocytospermic asymptomatic inflammatory prostatitis may be overlooked. We compared local and systemic OxS levels in male partners of infertile couples with different inflammation patterns in their genital tract and/or oligospermia. Subjects (n=143) were grouped according to inflammation in their semen, expressed prostatic secretion (EPS), and/or post-massage urine (post-M). Systemic (8-isoprostanes in urine) and local (diene conjugates and total antioxidant capacity in seminal plasma) OxS was measured The levels of OxS markers were significantly elevated in both severe inflammation groups--leukocytospermic men and subjects whose inflammation was limited only to EPS and/or post-M. Comparison between oligospermic and non-oligospermic men with genital tract inflammation, and oligozoospermic men with or without inflammation in the genital tract indicated that inflammation but not oligospermia status had significant impact on the measured OxS markers. Hence, a high leukocyte count in prostate-specific materials (EPS, post-M), even in absence of clear leukocytopsermia, is an important source of local and systemic OxS that may be associated with male infertility and affect general health. We suggest including the tests for detection of inflammation of the prostate into the workup of infertile men as was suggested in the WHO 1993 recommendation.

Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.

Background: Inflammatory prostatitis patients are characterized by oxidative stress (OxS) at local and systemic levels. Less is known about the occurrence of OxS in the case of other frequent male genital tract disorders., Methods: The study included 196 men: controls (n = 28), asymptomatic inflammatory (NIH category IV) prostatitis patients (n = 21), non-inflammatory (NIH category IIIb) chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients (n = 48), inflammatory (NIH category IIIa) CP/CPPS patients (n = 44), benign prostate hyperplasia (BPH) patients (n = 33), and patients with BPH and NIH IV category prostatitis (n = 22). In all subjects, 8-isoprostanes (8-EPI) in urine were determined by competitive enzyme-linked immunoassay., Results: The levels of 8-EPI were substantially higher in all diseased groups-inflammatory CP/CPPS (P < 0.001), non-inflammatory CP/CPPS (P = 0.03), asymptomatic inflammatory prostatitis (AIP; P = 0.02), BPH (P = 0.007), and BPH + AIP (P = 0.014) in comparison with controls. Importantly, our study showed that OxS is also present in the case of NIH IIIb category prostatitis when the patients have just chronic pelvic pain but no inflammation in prostate-specific materials, as well as in the patients with just lower urinary tract symptoms without pain or overt inflammation., Conclusions: This study revealed that several male genital tract disorders-BPH and different forms of prostatitis (NIH categories IIIa, IIIb, and IV)-are tightly interconnected via OxS-mediated pathways. Acknowledging OxS as an important pathogenesis mechanism of these diseases helps to open up new horizons for their treatment., (Copyright © 2011 Wiley Periodicals, Inc.)

Prostatitis is a disease that seriously affects the quality of patients' life. In the majority of cases, chronic prostatitis (chronic pelvic pain syndrome--CPPS) has an unclear pathogenesis. Anti-inflammatory and anti-infectious treatments have remained controversial. According to the latest research, prostatitis has been associated with oxidative stress (OxS) and/or OxS-related genetic polymorphisms. We have observed that prostatitis patients have systemic OxS in case of inflammation and pain. We propose a new explanation for the role of OxS in the pathogenesis of prostatitis and describe the putative OxS-related pathways in detail. The neural vicious circle starts by activation of primary sensory afferents. Glutamate mediates the signal to the neurons in the dorsal horn of the spinal cord, and facilitates calcium influx into their mitochondria. The latter causes an increased production of superoxide radicals. If the superoxide production is not effectively controlled by mitochondrial superoxide dismutase (Mn-SOD), then superoxide leads to OxS and lipid peroxidation. Consequent release of electrophilic lipid peroxidation products (LPP) from dorsal horn of the spinal cord causes pain by activating the primary sensory afferents, again. Additional LPP-mediated causes of pain include glutathione depletion and neuron sensitisation by isoprostanes. Excretion of LPP into urine may exert positive feedback as well. Currently, different information exists about chronic prostatitis (inflammation, pain, oxidative stress, neural sensitisation, lower urinary tract symptoms). The clear links between these data are actually absent. We propose that vicious circle based on LPP, especially isoprostanes, is the linking mechanism., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We aimed to elucidate the immunological (cytokines), biochemical (antioxidative), and patho-morphological responses in the gut and liver evoked by the addition of Lactobacillus fermentum ME-3 to ofloxacin (OFX) treatment in an experimental infection model of Salmonella enterica serovar Typhimurium. After challenge with S. Typhimurium and treatment according to different schemes, either with OFX and/or addition of L. fermentum ME-3, the mice were killed. Blood, liver, spleen, and small intestine samples were plated to detect S. Typhimurium and lactobacilli. Histological slides were prepared from the liver and ileum. The cytokines (IL-10, IFN-γ, and TNF-α), the glutathione peroxidase and reductase, the glutathione ratio, and the lipid peroxides (LPO) in mucosa of the small intestine and liver were estimated. The addition of L. fermentum ME-3 to OFX increased the eradication of S. Typhimurium from tested sites because of antagonistic and antioxidative properties, reduced the presence of typhoid nodules in the liver, and decreased the values of LPO. The immunological response included the reduction of pro-inflammatory cytokines interferon-γ and tumour necrosis factor-α and the increase in anti-inflammatory cytokine interleukin-10 in the livers of mice without typhoid nodules., (© 2010 The Authors. Journal Compilation © 2010 APMIS.)

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.

Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however, their causal relationship is not yet completely understood. Much attention has been given to the possibility that inflammation is a primary process of atherosclerosis and that OxS may be a by-product of the inflammatory process. We hypothesized, accordingly, that chronic systemic inflammation affects endothelial vasomotor function in the subclinical condition, whereas oxidative modifications are more involved in the structural stiffening of the arteries in atherosclerosis. The aim of our study was to test this hypothesis. Endothelial function and arterial stiffness were assessed non-invasively by pulse wave analysis, and blood/urinary samples were taken in 39 patients with peripheral arterial disease as well as in 34 controls. The patients showed significantly reduced endothelial function index (EFI) and increased augmentation index (AIx), as well as higher estimated aortic pulse wave velocity (PWV) and elevated values of the intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein, myeloperoxidase and urinary 8-iso-prostaglandin F2a (F2-IsoPs). There was an inverse association between EFI and ICAM-1 (R = -0.44, p = 0.009) in the controls, but not in the patients. Augmentation index and estimated aortic PWV correlated with F2-IsoPs only in the patients (R = 0.5, p = 0.001; R = -0.43, p = 0.006, respectively). After controlling for potential confounders, these associations remained significant. The study demonstrates that impairment of endothelial vasomotor capacity is affected by degree of inflammation in the subclinical condition, whereas arterial stiffening is determined by level of oxidative modifications in atherosclerosis.

Glutathione (GSH) is the major low-molecular weight antioxidant in mammalian cells. Thus, its analogues carrying similar and/or additional positive properties might have clinical perspectives. Here, we report the design and synthesis of a library of tetrapeptidic GSH analogues called UPF peptides. Compared to cellular GSH our designed peptidic analogues showed remarkably higher hydroxyl radical scavenging ability (EC(50) of GSH: 1,231.0 +/- 311.8 microM; EC(50) of UPF peptides: from 0.03 to 35 microM) and improved antiradical efficiency towards a stable alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical. The best of UPF peptides was 370-fold effective hydroxyl radical scavengers than melatonin (EC(50): 11.4 +/- 1.0 microM). We also found that UPF peptides do not influence the viability and membrane integrity of K562 human erythroleukemia cells even at 200 microM concentration. Dimerization of GSH and UPF peptides was compared in water and in 0.9% saline solutions. The results, together with an earlier finding that UPF1 showed protective effects in global cerebral ischemia model in rats, suggest that UPF peptides might serve both as potent antioxidants as well as leads for design of powerful non-peptidic antioxidants that correct oxidative stress-driven events.

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.

We investigated whether the oxidative stress (OS) caused by skin inflammation could reflect in the blood, in a 21-year-old female student sensitized to nickel, colophony and abitole with often relapsing allergic contact dermatitis (ACD). As glutathione redox ratio was increased in the blood not only during the relapse but also in the beginning of remission phase, we prescribed natural medical preparations of d-alpha-tocopherol (in the first week 100 mg three times a day followed by 100 mg/day) and ascorbic acid (200 mg/day) for 25 days to her. After using antioxidants in the remission period, one of the principal OS markers-the glutathione redox ratio reached the normal physiological level. In this report, we showed that during acute extensive ACD OS is expressed in the blood and simultaneous supplementation of d-alpha-tocopherol and ascorbic acid might reduce systemic OS.

Unlabelled: The purpose of this investigation was to measure the effect of ferrous iron therapy on indices of oxidative stress in pregnant women., Material and Methods: Nineteen healthy pregnant women with borderline anemia were subjected to per oral ferrous iron in prophylactic doses (36 mg daily, +Fe group, n=13) or did not get any treatment (-Fe group, n=6). The indices measured in two time-points were: conjugated dienes, lag phase of low-density lipoproteins, total antioxidant activity of the serum, total glutathione and its fractions, protein carbonyls, catalase, ferritin, serum iron and unsaturated iron binding capacity., Results: All women had high values of conjugated dienes, total antioxidant activity and short lag phases of low-density lipoproteins in both time points. Elevated values of oxidized glutathione in both groups increased about 2-fold and reached a significant difference level (p=0.02) by the end of the test period., Conclusion: Low doses of per oral ferrous iron did not change deleteriously the physiological pattern of parameters of oxidative stress in our small group of healthy pregnant non-smokers but the elevation of oxidized glutathione might imply on the elevation of risk.