Surrogate Marker Of Oxidative Stress Research Articles

Hyperuricemia and Its Association With the Severity and Complications of Congestive Heart Failure: A Systematic Review.

Several studies have shown that an association exists between hyperuricemia and heart failure. Despite several innovative management strategies, heart failure is a significant cause of mortality worldwide. Hyperuricemia in heart failure patients leads to poorer outcomes. Additionally, hyperuricemia can be a strong surrogate marker for increased oxidative stress in heart failure patients. This oxidative stress leads to vascular endothelial damage and is linked to worsening heart failure and subsequent mortality. Hence, the measurement of serum uric acid levels in these patients can predict the present and future risk of complications of heart failure. Despite this knowledge, serum uric acid levels are not usually followed up in heart failure patients. This systematic review aims to give additional clarity to this association. We used research from the last twenty years (2002 to 2022) obtained from databases such as PubMed, PubMed Central (PMC), Google Scholar, and Science Direct. We used the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guidelines. We removed duplicates, screened articles on the basis of title and abstract, applied eligibility criteria, and performed quality appraisal. Eventually, 15 articles were selected for review. There were 12 observational studies, two randomized controlled trials, and one meta-analysis. Our review showed that serum uric acid elevation is associated with the severity and complications of congestive heart failure. Serum uric acid can serve as a useful surrogate marker of oxidative stress in congestive heart failure (CHF) patients. The role of xanthine oxidase inhibitors needs to be evaluated further in CHF patients.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Tear Lactate Levels as a Surrogate Marker of Oxidative Stress in Myopia: A Case-control Study

Introduction: Myopia is most common refractive error leading to visual dysfunctions worldwide. Oxygen deficit due to environmental stress leads to increase in anaerobic glycolysis which results in lactate production. Increase in Reactive Oxygen Species (ROS) and inability of defense system to eliminate them is also responsible for alteration of regulatory pathways. The patient with elevated lactate levels are at significant risk of morbidity and hence, require a prompt treatment. Aim: To estimate and study the lactate levels in tear in various degree of myopia. Materials and Methods: This case-control study was conducted in tertiary care center, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India. Twenty five patients each with low, medium, high myopia, age and sex matched healthy controls (i.e, Group 1-4). Diagnosis was established with help of detailed history, clinical and ocular examination. Lactate levels were estimated in tear samples by enzymatic method on autoanalyzer within 30 minutes of collection. Independent Student’s t-test was used to determine the significance between myopia and controls. Results: Out of total 100 subjects, 68% were males and 32% were females. The mean±SD age was 24.56±6.35, 24.12±5.45, and 23.24±5.17, 21.69±3.95 in the Group 1, Group 2, Group 3 and Group 4 respectively in the control group, group with low, medium and high myopia respectively which was statistically not significant. The results of this study showed that lactate levels in tears were significantly higher (p-value=0.013) in myopia patients as compared to controls (1.34±0.46 versus 1.06±0.50). Additionally, the lactate levels increased with the progression of degree of myopia. Conclusion: Increase in the level of lactate in tear was directly proportional to the degree of myopia. Tear lactate levels can be used as a non invasive method to study oxidative stress in individuals. Further studies with more oxidative markers in tears can also be compared with blood values in larger groups of patients with long-term follow-up to validate the finding.

Albumin Oxidation Status in Sepsis Patients Treated With Albumin or Crystalloids.

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercapto-albumin (HMA), human non-mercapto-albumin form 1 (HNA1) and human non-mercapto-albumin form 2 (HNA2)] in 60 patients with severe sepsis or septic shock and 21 healthy controls. The sepsis patients were randomized (1:1) to treatment with 20% albumin and crystalloid solution or crystalloid solution alone. The albumin oxidation forms were measured at day 1 and day 7. To assess the albumin oxidation forms as a function of oxidative stress, the 60 sepsis patients, regardless of the treatment, were grouped based on baseline sequential organ failure assessment (SOFA) score as surrogate marker of oxidative stress. At day 1, septic patients had significantly lower levels of HMA and higher levels of HNA1 and HNA2 than healthy controls. HMA and HNA1 concentrations were similar in patients treated with albumin or crystalloids at day 1, while HNA2 concentration was significantly greater in albumin-treated patients (p < 0.001). On day 7, HMA was significantly higher in albumin-treated patients, while HNA2 significantly increased only in the crystalloids-treated group, reaching values comparable with the albumin group. When pooling the septic patients regardless of treatment, albumin oxidation was similar across all SOFA groups at day 1, but at day 7 HMA was lower at higher SOFA scores. Mortality rate was independently associated with albumin oxidation levels measured at day 7 (HMA log-rank = 0.027 and HNA2 log-rank = 0.002), irrespective of treatment group. In adjusted regression analyses for 90-day mortality, this effect remained significant for HMA and HNA2. Our data suggest that the oxidation status of albumin is modified according to the time of exposure to oxidative stress (differences between day 1 and day 7). After 7 days of treatment, lower SOFA scores correlate with higher albumin antioxidant capacity. The trend toward a positive effect of albumin treatment, while not statistically significant, warrants further investigation.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians.

Both nutrition and exercise are known to affect metabolic regulation in humans. Sirtuins are essential regulators of cellular energy metabolism; SIRT1, SIRT3, and SIRT4 have a direct effect on glycolysis, oxidative phosphorylation, and fatty acid oxidation. This cross-sectional study investigates the effect of different diets on exercise-induced regulation of sirtuins. SIRT1 and SIRT3–SIRT5 were measured in blood from omnivorous, lacto-ovo vegetarian, and vegan recreational runners (21–25 subjects, respectively) before and after exercise at the transcript, protein, and enzymatic levels. SIRT1, SIRT3, and SIRT5 enzyme activities increased during exercise in omnivores and lacto-ovo vegetarians, commensurate with increased energy demand. However, activities decreased in vegans. Malondialdehyde as a surrogate marker of oxidative stress inversely correlated with sirtuin activities and was elevated in vegans after exercise compared to both other groups. A significant negative correlation of all sirtuins with the intake of the antioxidative substances, ascorbate and tocopherol, was found. In vegan participants, increased oxidative stress despite higher amounts of the antioxidative substances in the diet was observed after exercise.

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAT) compared to subcutaneous sites (SAT) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAT or SAT amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRI-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAT and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

To assess the relevance of lipoprotein-associated phospholipase A2activity as a diagnostic andprognostic marker for renalmicrovascular diseases. We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up(DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

SUN-081 Eicosapentaenoic Acid Administration Ameliorates Cardiac Remodeling In Humans And Protects Against Ang Ii-induced Cardiovascular Remodeling Via Attenuation Of Oxidative Stress In Mice.

Background & Objective: Eicosapentaenoic acid (EPA), the major n-3 polyunsaturated fatty acid, reduces risk of cardiovascular events. However, the molecular mechanism underlying the cardiovascular protection by EPA remains unclear. Therefore, we evaluated the clinical effects of EPA against cardiac remodeling in subjects with cardiovascular risk factors and assessed mechanisms of EPA in cardiovascular remodeling of an angiotensin II-treated mouse model. Methods & Results: Clinical study: A total of 25 Japanese subjects were orally administered purified EPA (average dosage of 1630 mg per day) and underwent echocardiographic examinations before and after medication (average observation period of 14 months). Although EPA treatment did not affect left ventricular systolic function, EPA supplementation reduced left ventricular mass index (103.1±23.4 to 98.4±22.3 g/m2, p<0.05) and ameliorated the ratio of peak E velocity to early diastolic mitral annulus velocity (E/e' ratio) (10.73±3.95 to 7.77±2.76, P<0.01) as a surrogate marker of left ventricular diastolic dysfunction. Animal study: Eight-week-old C57BL/6 male mice were fed normal diet chow (control group) or EPA-rich diet (5% EPA) (EPA group) and infused with angiotensin II (Ang II) (2.0 mg/kg/day) for 14 days. Ang II stimulation markedly increased medial thickness and perivascular fibrosis of the coronary artery and aorta and caused cardiac concentric change with increased interstitial cardiac fibrosis in the control group; however, EPA administration significantly ameliorated those Ang II-induced cardiovascular adverse phenotypes. In addition, EPA administration reduced surrogate markers of oxidative stress, such as urinary excretion of 8-hydroxy-2'-deoxyguanosine, plasma level of derivatives of reactive oxygen metabolites and cardiovascular superoxide production with attenuation of gene expression levels of NADPH oxidase components, including p22 phox and p67 phox, and Rac1 activation. Conclusions: EPA administration ameliorates cardiac remodeling in humans and protects against Ang II-induced cardiovascular remodeling via attenuation of oxidative stress in mice.

A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl stress.

Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently used as surrogate markers of oxidative stress in obesity. A pathogenic role for RCS in metabolic diseases of obesity remains controversial, however, partly because of their highly diffuse and broad reactivity and the lack of specific RCS-scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine and carnosine) show RCS reactivity, but their therapeutic potential in humans is limited by serum carnosinases. Here, we present the rational design, characterization, and pharmacological evaluation of carnosinol, i.e., (2S)-2-(3-amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, a derivative of carnosine with high oral bioavailability that is resistant to carnosinases. Carnosinol displayed a suitable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and was determined to have the greatest potency and selectivity toward α,β-unsaturated aldehydes (e.g., 4-hydroxynonenal, HNE, ACR) among all others reported thus far. In rodent models of diet-induced obesity and metabolic syndrome, carnosinol dose-dependently attenuated HNE adduct formation in liver and skeletal muscle, while simultaneously mitigating inflammation, dyslipidemia, insulin resistance, and steatohepatitis. These improvements in metabolic parameters with carnosinol were not due to changes in energy expenditure, physical activity, adiposity, or body weight. Collectively, our findings illustrate a pathogenic role for RCS in obesity-related metabolic disorders and provide validation for a promising new class of carbonyl-scavenging therapeutic compounds rationally derived from carnosine.

Altered levels of serum Copper, Magnesium as a marker of oxidative stress in Predicting Systemic Inflammation in Type 2 Diabetes

Introduction: Diabetes Mellitus is a metabolic disease characterized by hyperglycemia due to defective insulin secretion or action. Trace elements like Copper(Cu) and magnesium (Mg) have been found to be altered in diabetes mellitus and induce reactive oxygen species which has got role in progression of disease. Malondialdehyde (MDA) is a surrogate marker of oxidative stress in type 2 diabetes mellitus. Aims And Objectives: Propose of the study was to estimate serum magnesium (Mg), copper and MDA levels in type 2 diabetes mellitus patients and to compare with that of healthy individuals, also to identify the interrelationship among these and copper &magnesium can be used as an alternate marker of oxidative stress when MDA not available. Materials And Methods:The study included 75 control healthy individuals without Type2 DM and 75 Cases with type 2 DM. Serum concentrations of Glucose, Total Cholesterol, Triglycerides, LDL-C, HDL-C, HbA1c, Magnesium, Copper and MDA was measured. Student's t-test, Pearson correlations tests were used for statistical analysis. Results And Observations: The serum copper level was found to be significantly increased in type 2 DM with HbA1C >7% (157.32±16.89) when compared to control (106.24±25.99). The serum Mg level was found to be significantly decreased (1.62±0.29) (p 7 when compared to control (1.82±0.18). We found a significant increased level of serum Total Cholesterol and LDL-c and Triglycerides and decreased HDL-c in type 2 DM subjects with (p 7% when compared to control. MDA (4.62+1.17nmol/L) in type 2 DM patients when compared to controls(1.4+0.8 nmol/L)( p< 0.0001). Overall, mean serum MDA level in the study group was significantly higher than in the controls. Conclusion: Patients with DM had altered metabolism of Cu (hypercuprimiea) and Mg (hypomagnesaemia). As Cu and Mg has got role in metal induced free radical formation which leads to oxidative stress we compared with novel oxidative marker MDA and concluded that these two trace elements can be used as marker of oxidative stress, which can predict systemic inflammation in type 2 DM to prevent well know complication in advance

Relationship between obstructive sleep apnea and endogenous carbon monoxide

Endogenous carbon monoxide (CO) levels are recognized to be a surrogate marker of oxidative stress. No study has evaluated both exhaled and blood CO at the same time in obstructive sleep apnea (OSA) patients. Here we provide evidence that exhaled CO levels positively correlated with hypoxia during sleep in OSA patients, but blood CO levels did not, and that continuous positive airway pressure therapy significantly decreased exhaled CO levels in the OSA group, but did not significantly affect blood CO.

Plasma heme oxygenase-1 is decreased in peripheral artery disease patients.

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. A number of emerging risk factors, including oxidative stress biomarkers, free radicals and heat shock proteins, may add to the established risk factors for cardiovascular disease (CVD). The present study assessed surrogate markers of oxidative stress, including total reduced glutathione (GSH), lipid hydroperoxides (LOOH), isoprostanes, heme oxygenase‑1 (HO‑1) and metabolic biomarkers, such as adiponectin and lactate, in PAD patients (n=27). Healthy age‑matched volunteers (n=27) served as controls. GSH and LOOH were evaluated by measuring total thiol groups and iron oxidation, respectively, by spectrophotometric analysis. Adiponectin, isoprostanes and HO‑1 levels were determined using commercially available ELISA kits and lactate level was determined colorimetrically. Results from patients with PAD demonstrated no significant difference in GSH content and LOOH formation when compared with healthy controls (5.1±7.6vs.6.9±9.1nmol/ml and 6.8±14.2vs.8.3±14.9nmol/ml, respectively), however, isoprostanes were demonstrated to be significantly reduced (3.8±4.8pg/mlvs.120±91pg/mll; P<0.001). Furthermore, HO‑1, a protective heat shock protein, was significantly reduced in PAD patients (0.8±0.7vs.3.4±1.3ng/ml; P<0.001). Adiponectin, an antiatherogenic adipokine, was not significantly different between the two groups (1.4±0.2vs.1.5±0.5µg/ml), whereas serum lactate was significantly higher in PAD patients compared with controls (0.11±0.01vs.0.1±0.01mM; P<0.05). Using multivariate analysis, HO‑1, hypertension, smoking and dyslipidemia were indicated to be independently associated with the presence of PAD, while only ankle‑brachial index was an independent predictor of severity of PAD. The oxidative pathway may be partially involved in the onset and progression of PAD and may represent a target to reduce the risk of ischemic events.

P35. Novel interaction of placental caveolin-1 expression with markers of oxidative stress and the renin-angiotensin system (RAS) in pre-eclampsia

Introduction Caveolin-1 (cav-1) is one of the major protein components of caveolae required for the coordination of some signalling pathways, including that of angiotensin II (AngII) with its Type 1 receptor (AT1R). We have previously reported decreased cav-1 and increased AT1R protein expression in placentae from women with pre-eclampsia (PE). Within the PE placenta, an increase in AngII acting via AT1R may lead to increased vasoconstriction, but possible functional effects of altered cav-1, and interactions with components of RAS and markers of oxidative stress have not been investigated. Objective To establish mechanistic interactions of placental cav-1 with RAS components and surrogate markers of oxidative stress and antioxidant concentrations. Methods Immunohistochemistry was performed on paraffin-embedded serial placental sections from 24 normotensive (NC) and 19 women with PE, using antibodies to cav-1, prorenin receptor (PRR), angiotensinogen (AGT), AT1R, AngII type 2 receptor (AT2R) and eNOS. Protein expression was semi-quantitatively assessed and also analysed with respect to previously measured maternal plasma TBARS (Thiobarbituric acid-reactive substances) concentration and placental glutathione peroxidase (GPx) activity. Results Positive correlations were observed between placental expression of cav-1 and the AT2R ( P = 0.003) and PRR ( P P > 0.7, P > 0.5). However, cav-1 was inversely correlated with eNOS expression in both NC and PE placentae ( P P = 0.003). No significant correlations were observed with AGT or AT1R. A negative correlation was observed between maternal TBARS and cav-1 protein ( P = 0.003), and between placental GPx activity and cav-1 protein ( P = 0.027) only in the PE placentae. Conclusions A complex cascade links activation of the AT1R with NADPH oxidase activation, generation of reactive oxygen species (ROS), the uncoupling of eNOS and subsequent modification of redox-sensitive caveolar proteins in vascular smooth muscle outside pregnancy. Our findings suggest that this cascade is altered in hypertensive pregnancy, in a direction which would lead to enhanced local vasoconstriction.

Nocturnal non-dipping hypertension – A clinical surrogate marker of oxidative stress and cardiovascular adversity

Nocturnal non-dipping hypertension – A clinical surrogate marker of oxidative stress and cardiovascular adversity

Association between serum uric acid and atrial fibrillation: A systematic review and meta-analysis

Atrial fibrillation (AF) is mediated by oxidative stress, neurohormonal activation, and inflammatory activation. Serum uric acid (SUA) is a surrogate marker of oxidative stress. Xanthine oxidase produces SUA and is upregulated by inflammation and neurohormones. To perform a meta-analysis to evaluate the evidence supporting an association between AF and SUA. We searched the MEDLINE database (1966 to 2013) supplemented by manual searches of bibliographies of key relevant articles. We selected all cross-sectional and cohort studies in which SUA was measured and AF was reported. In cross-sectional studies, we calculated the pooled standardized mean difference of SUA between those with AF and those without AF. In cohort studies, we calculated the pooled relative risk with the corresponding 95% confidence interval (CI) for incident AF by using the random effects method. The search strategy yielded 40 studies, of which only 9 met our eligibility criteria. The 6 cross-sectional studies comprised 7930 evaluable patients with a median prevalence of heart failure of 4% (IQR 0%-100%). The standardized mean difference of SUA for those with AF was 0.42 (95% CI 0.27-0.58) compared with those without AF. The 3 cohort studies evaluated 138,306 individuals without AF. The relative risk of having AF for those with high SUA was 1.67 (95% CI 1.23-2.27) compared with those with normal SUA. High SUA is associated with AF in both cross-sectional and cohort studies. It is unclear whether SUA represents a disease marker or a treatment target.

Does Short-Term Vitamin C Reduce Cardiovascular Risk in Type 2 Diabetes?

Vitamin C is a powerful antioxidant that is potentially useful in the prevention of atherosclerosis in diabetic individuals. However, the mechanism(s) of vitamin C's anti-atherosclerotic effects in vivo are unresolved, and clinical trials in nondiabetic individuals have yielded conflicting results. Therefore, we performed 32 studies in a randomized, crossover, dose-response trial in 8 volunteers with type 2 diabetes to determine the effects of vitamin C on serum vitamin C levels, lipids, inflammation, and coagulation. Well-controlled, type 2 volunteers received, in randomized order for 2-week periods, each of the following: 1) no supplemental vitamin C, 2) low-dose vitamin C (250 mg/day), 3) medium-dose vitamin C (500 mg/day), and 4) high-dose vitamin C (1,000 mg/day). A high-caloric content lunch was ingested during each study arm to enhance oxidative stress. Serum vitamin C levels and atherosclerotic risk factors including lipids and markers of oxidative stress, inflammation, and hypercoagulation were determined. Serum vitamin C levels increased significantly at all dosages. In addition, the high-caloric content meal resulted in acute elevations of glucose, insulin, and triglycerides for several hours postmeal. However, no significant effect of vitamin C was observed on lipid parameters or any of the surrogate markers of oxidative stress, inflammation, or hypercoagulability. Our study suggests that if vitamin C does have anti-atherosclerotic effects in diabetes, it does not exert them through the traditional pathways identifiable by established surrogate markers of cardiovascular risk.

Glycaemic variability in paediatric patients with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI): a cross‐sectional cohort study

This cross-sectional observational cohort study was designed to investigate i) whether glycaemic variability in paediatric patients with type 1 diabetes is lower in those using an insulin pump (CSII) compared with those using multiple daily insulin injections (MDI) and ii) whether urinary F2 -isoprostanes and/or urinary prostaglandin F2 excretion as surrogate marker of oxidative stress and cyclooxygenase activity are associated with glycaemic variability. 48 paediatric patients with type 1 diabetes (22 using an insulin pump) underwent an ambulatory 3-day continuous glucose monitoring. All patients continued with normal daily activities and collected urine for two consecutive 24 h periods. The glucose pentagon was used to calculate the glycaemic risk parameter. Insulin requirements, HDL-cholesterol, the mean of glycaemic excursions (P < 0·01) and the standard deviation of mean glucose concentration (P < 0·05) were significantly lower in patients with CSII compared with those using MDI. By contrast, averaged HbA1c during the last twelve months as well as at the time of sensor insertion did not differ significantly between both groups. Summarizing characteristic parameter of acute and long-term metabolic control into the glucose pentagon revealed a significantly lower glycaemic risk parameter in CSI patients compared with both, healthy subjects and patients using MDI (P < 0·05). Paediatric patients with type 1 diabetes using an insulin pump presented with lower glycaemic variability and a concomitantly lower glycaemic risk parameter compared with those using MDII. Whether these findings translate into a lower risk of diabetes associated cardiovascular complications remains to be elucidated.

Reduced plasmalogen concentration as a surrogate marker of oxidative stress in elderly septic patients

Severe sepsis is reportedly accompanied by oxidative stress with a depletion of antioxidant defense. We estimated plasmalogen vinyl ether bond (PVEB) levels in blood plasma of 20 elderly patients with initial severe sepsis, serving as a sensitive surrogate marker of oxidative stress, and compared them with standard markers, i.e., Acute Physiology and Chronic Health Evaluation (APACHE) II score, C-reactive protein (CRP), creatinine, white blood cell and platelet counts. Patients were included in the study and then blood samples were taken within 24h of the onset of symptoms of severe sepsis. Twenty sex- and age-matched, healthy individuals were included in the study as controls. We measured plasmalogen-derived hexadecanal dimethyl acetal (16:0 DMA) in isolated phospholipids from EDTA-plasma using gas chromatography. We found a 55% lower concentration of 16:0 DMA, corresponding to lower levels of PVEB in the patients’ plasma compared to the controls (0.26±0.15 vs 0.58±0.13g/100g; p<0.001). In all patients’ and non-survivors’ samples the 16:0 DMA levels correlated negatively with plasma CRP values (RS=−0.48 and RS=−0.70, respectively; p<0.05), but not with APACHE II scores or other markers. The observed lower baseline content of PVEB may indicate oxidative stress contributing to the sequlae of sepsis, but did not correlate with the outcome or the severity of illness. Serial measurements are needed to validate PVEB as a marker in sepsis.

Assessment of Reproducibility of Exhaled Hydrogen Peroxide Concentration and the Effect of Breathing Pattern in Healthy Subjects

Hydrogen peroxide (H2O2) is detectable in exhaled breath condensate (EBC) and has been proposed to be a surrogate marker of oxidative stress in the airways. In this study we tested whether the breathing pattern during EBC collection influences the concentration of exhaled H2O2. EBC was collected during (1) tidal breathing and (2) breathing with increased tidal volume for 10 min from 16 healthy volunteers. On-line H2O2 measurement was performed by the EcoCheck™ biosensor system. Repeated measurements were also conducted to assess intrasubject reproducibility. Minute ventilation, tidal volume, expiratory flow rate were all increased significantly when subjects were asked to perform breathing with increased tidal volume. In parallel, EBC volume increased (1413±59 vs. 1959±71 μL, p<0.001), whereas exhaled H2O2 levels decreased significantly (1400±170 vs. 840±130 nmol/L, p<0.001). H2O2 levels did not correlate with any individual breathing parameters (p>0.05). Assessment of intersubject variability of H2O2 measurements during the two types of breathing revealed a coefficient of variation of 49 and 54%, respectively. The EBC H2O2 measurement was highly reproducible (888±176 vs. 874±156 nmol/L) as tested during normal breathing. These data demonstrate that the concentration of H2O2 in EBC depends on the ventilatory pattern during sample collection that has to be taken into consideration in all EBC H2O2 assays.