Brachial artery intima-media thickness and echogenicity in relation to lipids and markers of oxidative stress in elderly subjects:--the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) Study.
The aim of the present study was to relate brachial artery intima-media thickness (IMT) and the grey scale median of the intima-media complex (IM-GSM) to traditional cardiovascular risk factors and markers of inflammation and oxidative stress. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, brachial artery IMT and IM-GSM, who were evaluated by ultrasound. Lipids, thirteen markers of inflammation and nine markers of oxidative stress were measured. The Framingham risk score was related to IMT (p
Cadmium in urine is positively associated with urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentrations, a sensitive marker of oxidative DNA damage. We determined whether kidney concentrations of cadmium, mercury, and lead, which may generate oxidative DNA damage, were associated with urinary 8-oxodG or not.
8-OxodG was measured in separate 24 h and overnight urine samples from Swedish healthy adult kidney donors (N = 152) using LC-MS/MS. Concentrations of metals were measured in kidney biopsies (N = 109) by ICP-MS.
The median 8-oxodG concentrations (adjusted to specific gravity) in 24 h and overnight samples were 13.5 and 15.3 nmol/L; 8-oxodG excretion rates in 24 h and overnight samples were 0.93 and 0.86 nmol/h. In multivariable linear regression analyses, we did not find any association between 8-oxodG concentrations or rates and elements in the kidney. The 24-h 8-oxodG concentrations were positively associated with serum ferritin (ß = 0.048, p
Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.
BACKGROUND: Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. METHODS: The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. RESULTS: In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. CONCLUSION: The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall.
In military outdoor shooting training, with safety measures enforced, the risk of a permanent, noise-induced hearing loss is very small. But urban warfare training performed indoors, with reflections from walls, might increase the risk. A question is whether antioxidants can reduce the negative effects of noise on human hearing as it does on research animals. Hearing tests were performed on a control group of 23 military officers before and after a shooting session in a bunker-like room. The experiments were repeated on another group of 11 officers with peroral adminstration of N-acetyl-cysteine (NAC), directly after the shooting. The measurements performed were tone thresholds; transient-evoked otoacoustic emissions, with and without contralateral noise; and psycho-acoustical modulation transfer function (PMTF), thresholds for brief tones in modulated noise. Effects from shooting on hearing thresholds were small, but threshold behavior supports use of NAC treatment. On the PMTF, shooting without NAC gave strong effects. Those effects were like those from continuous noise, which means that strict safety measures should be enforced. The most striking finding was that the non-linearity of the cochlea, that was strongly reduced in the group without NAC, as manifested by the PMTF-results, was practically unchanged in the NAC-group throughout the study. NAC treatment directly after shooting in a bunkerlike room seems to give some protection of the cochlea.
BACKGROUND: Chronic heart failure (CHF) is a complex syndrome, in which reactive oxygen species and inflammatory cytokines are important stressors that contribute to the pathogenesis. AIM: We have studied physiological stress response parameters in CHF, in particular the redox-active regulator thioredoxin. SUBJECTS: A case-control study was conducted including a consecutive sample of CHF patients (n=27) of NYHA class II and III; comparison control subjects (n=29) were recruited from an association for retired people. METHOD: Baseline levels of Trx, lipid peroxides (oxidative stress), TNF and IL-6 cytokines, platelet-activation marker P-selectin, cortisol (as peripheral effector of HPA axis), and the potent antioxidant selenoprotein Trx-reductase were assessed. RESULTS: Mean (+/-S.E.M.) plasma levels of Trx were significantly higher in patients with CHF (32+/-3 ng/ml), than in the healthy subjects (12+/-3 ng/ml, PNYHA class II) and degree of stress. Trx elevation correlated well with increased oxidative stress (lipid peroxides, P
Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO(2max) 65 Â± 1 ml/kg/min, W max 387 Â± 8 W) exercised for 60 min at approximately 64 % VO(2max) with either low [166 Â± 21 mmol/kg dry weight (dw)] or normal (478 Â± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-? coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.
To identify changes in gene expression in the airways among welders, with and without lower airway symptoms, working in black steel.
Included were 25 male, non-smoking welders. Each welder was sampled twice; before exposure (after vacation), and after 1 month of exposure. From the welders (14 symptomatic, of whom 7 had asthma-like symptoms), RNA from induced sputum was obtained for gene expression analysis. Messenger RNA from a subset of the samples (n = 7) was analysed with microarray technology to identify genes of interest. These genes were further analysed using quantitative PCR (qPCR; n = 22).
By comparing samples before and after exposure, the microarray analysis resulted in several functional annotation clusters: the one with the highest enrichment score contained "response to wounding", "inflammatory response" and "defence response". Seven genes were analysed by qPCR: granulocyte colony-stimulating factor 3 receptor (CSF3R), superoxide dismutase 2, interleukin 8, glutathione S-transferase pi 1, tumour necrosis factor alpha-induced protein 6 (TNFAIP6), interleukin 1 receptor type II and matrix metallopeptidase 25 (MMP25). Increased levels of CSF3R, TNFAIP6 and MMP25 were indicated among asthmatic subjects compared to non-symptomatic subjects, although the differences did not reach significance.
Workers' exposure to welding fumes changed gene expression in the lower airways in genes involved in inflammatory and defence response. Thus, microarray and qPCR technique can demonstrate markers of exposure to welding fumes and possible disease-related markers. However, further studies are needed to verify genes involved and to further characterise the mechanism for welding fumes-associated lower airway symptoms.
Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Central blood pressure (BP) is thought to be more relevant than peripheral BP for the pathogenesis of CVD. Advanced oxidation protein products (AOPP) are markers of oxidative stress. This study investigated the relationship between AOPP and central BP in peritoneal dialysis (PD) patients. ?
In a cross-sectional study of 75 PD patients (67% men), we analyzed two oxidative stress markers, AOPP (modified assay, mAOPP, correcting for the impact of triglycerides) and pentosidine, three inflammation markers, interleukin-6 (IL-6), tumor necrosis factor (TNF), and high-sensitivity C-reactive protein (hs-CRP). All patients underwent measurement of central systolic blood pressure (SBP) and diastolic blood pressure (DBP) by applanation tonometry. ?
Patients with mAOPP levels above the median had a higher central SBP and DBP than those below the median values. In univariate analysis, the levels of mAOPP associated with central SBP and central DBP. Multiple regression analysis, adjusting for age, gender, diabetes, CVD, protein-energy wasting (PEW), hs-CRP and extracellular water by multi-frequency bioimpedance or N-terminal prohormone of brain natriuretic peptide (NT-proBNP), confirmed independent associations between mAOPP and central SBP and central DBP respectively. ?
The mAOPP level is independently associated with the central SBP and DBP in PD patients. This finding suggests that oxidative stress may be involved in the pathogenesis of hypertension or that hypertension itself or factors associated with hypertension such as fluid overload may have an additional effect on oxidative stress in PD patients.
Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.
Cites: Recent Pat CNS Drug Discov. 2010 Jun;5(2):147-6320167005
Cites: Int J Cancer. 2010 Jul 1;127(1):172-8419876916