Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens.

OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. RESULTS: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). CONCLUSIONS: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

Allergic contact dermatitis is associated with significant oxidative stress.

Background. Research has confirmed the involvement of oxidative stress (OxS) in allergic contact dermatitis whilst other inflammation-related biomarkers have been less studied. Objective. To evaluate systemic levels of selected inflammatory markers, OxS indices and adipokines as well as their associations in allergic contact dermatitis. Methods. In 40 patients, interleukin- (IL-) 6, monocyte chemoattractant protein (MCP-1), and IL-10 levels were measured in sera with the Evidence Investigator Cytokine & Growth factors High-Sensitivity Array, total peroxide concentration (TPX) and total antioxidant capacity (TAC) by means of spectrophotometry, and the plasma concentrations of adiponectin and leptin by the quantitative sandwich enzyme immunoassay technique. Results. TNF-α level (P < 0.01) and TPX (P < 0.0001) were increased whilst IL-10 (P < 0.05) and TAC (P < 0.0001) were decreased in the patients as compared to controls. Correlation and multiple linear regression analysis identified both, TPX and TAC (inversely), as possible independent markers for evaluating allergic contact dermatitis. Adiponectin level in patients was increased (P < 0.0001), but neither adiponectin nor leptin correlated significantly with the biomarkers of inflammation or OxS. Conclusion. OxS parameters, especially TPX and OSI, reflect the degree of systemic inflammation associated with allergic contact dermatitis in the best way. The relation between OxS and adiponectin level warrants further studies.

Comparative study of systemic inflammatory responses in psoriasis vulgaris and mild to moderate allergic contact dermatitis.

BACKGROUND: Psoriasis vulgaris (PV) is associated with low-grade systemic inflammation. OBJECTIVE: Cytokines' and growth factors' serum patterns in patients with PV, allergic contact dermatitis (ACD) and healthy subjects were investigated to describe and compare systemic inflammatory responses in these diseases. METHODS: A total of 12 inflammation-sensitive biomarkers were analyzed simultaneously by means of the Evidence Investigator™ biochip technology. RESULTS: In PV, proinflammatory tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukins (IL)-1ß, -2, -6, -8, and monocyte chemoattractant protein (MCP)-1 were elevated. In ACD, 2 markers, TNF-α and MCP-1, were increased, and regulatory cytokine IL-10 was decreased. Proinflammatory IL-2 had the strongest correlations with other pro- as well as anti-inflammatory cytokines in PV and ACD, whilst IL-6 correlated positively with the Psoriasis Area and Severity Index. Growth factors' levels correlated with MCP-1, but only in PV. CONCLUSION: Although psoriasis induces a more variegated proinflammatory systemic response, ACD is likewise associated with a systemic increase in inflammatory mediators.

The levels of adiponectin and leptin and their relation to other markers of cardiovascular risk in patients with psoriasis.

BACKGROUND: A link between psoriasis and risk for cardiovascular disease (CVD) is supposed. Adipokines (adiponectin and leptin) playing roles in inflammation as well as lipid metabolism could have impact on CVD. OBJECTIVES: We investigated links between adiponectin and leptin levels and several inflammation- and oxidative stress-related CVD risk makers in patients with psoriasis. METHODS: Sixty patients with plaque-type psoriasis with normal total cholesterol levels belonging to three body mass index (BMI) categories: BMI < 24.9, BMI 25.0-29.9 and BMI ≥ 30.0 kg/m(2) were studied. Fasting blood samples were analysed for adiponectin, leptin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), oxidized low density lipoprotein (oxLDL), oxidized LDL/ß(2) -glycoprotein complexes (oxLDL-ß(2)-GPI) and standard blood lipid panel. RESULTS: In patients, adiponectin was negatively (P < 0.005), and leptin, oxLDL and oxLDL-ß(2) -GPI levels were positively correlated to BMI (P < 0.005, P < 0.05, and P < 0.01, respectively). Patients had higher hsCRP and IL-6 levels as compared with the endemic reference values. High adiponectin was strongly associated with higher TNF-α and high density lipoprotein cholesterol (P = 0.001), and lower triglycerides (TG) (P = 0.01) as well as oxLDL-ß(2) -GPI levels (P < 0.05). After multivariate adjustment, the association for TNF-α and TG remained significant (P < 0.01 for both). Multiple regression analysis also revealed that leptin concentration was significantly associated with hsCRP, oxLDL and TG levels. CONCLUSION: The data suggest that in addition to the strong effect of inflammation and LDL oxidation, adipokine level may be one of the mechanisms behind the close association between psoriasis and CVD. Given the significant relations of several markers with BMI, health consequences of excessive weight should be better communicated to patients with psoriasis.

Relation of exploratory behaviour to plasma corticosterone and Wfs1 gene expression in Wistar rats.

Male Wistar rats exhibit significant variations in exploratory behaviour in the elevated plus-maze (EPM) model of anxiety. We have now investigated the relation between exploratory behaviour and levels of corticosterone and systemic oxidative stress. Also, the expression levels of endocannabinoid-related and wolframin (Wfs1) genes were measured in the forebrain structures. The rats were divided into high, intermediate and low exploratory activity groups. Exposure to EPM significantly elevated the serum levels of corticosterone in all rats, but especially in the high exploratory group. Oxidative stress indices and expression of endocannabinoid-related genes were not significantly affected by exposure to EPM. Wfs1 mRNA level was highly dependent on exploratory behaviour of animals. In low exploratory activity rats, Wfs1 gene expression was reduced in the temporal lobe, whereas in high exploratory activity group it was reduced in the mesolimbic area and hippocampus. Altogether, present study indicates that in high exploratory activity rats, the activation of brain areas related to novelty seeking is apparent, whereas in low exploratory activity group the brain structures linked to anxiety are activated.

Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis.

BACKGROUND: Several studies have shown increased prevalence of obesity in patients with psoriasis. OBJECTIVES: To characterize both inflammatory- and oxidative stress-related differences between obese patients with psoriasis (OPP) and normal-weight patients with psoriasis (NWPP). METHODS: The plasma concentrations of adiponectin and interleukin (IL)-6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI)<25 and 12 patients with a BMI>30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically. RESULTS: Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal-weight controls (P<0.001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL-6 level, which correlated negatively with the adiponectin level (r=-0.85, P<0.001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r=-0.63, P<0.05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls. CONCLUSIONS: Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.

Oxidative stress in leucocytospermic prostatitis patients: preliminary results.

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

17beta-Oestradiol stimulation of G-proteins in aged and Alzheimer's human brain: comparison with phytoestrogens.

The neuroprotective action of oestrogens and oestrogen-like compounds is in the focus of basic and clinical research. Although such action has been shown to be associated with neuronal plasma membranes, the implication of G-proteins remains to be elucidated. This study revealed that micromolar concentrations (microM) of 17beta-oestradiol and phytoestrogens, genistein and daidzein, significantly (P < 0.05) stimulate G-proteins ([(35)S]GTP gamma S binding) in the post-mortem hippocampal membranes of age-matched control women with the respective maximum effects of 28, 20 and 15% at 10 microM. In the frontocortical membranes, the stimulation of G-proteins did not differ significantly from that in hippocampal membranes. Although in the hippocampus and frontal cortex of the Alzheimer's disease (AD) women's brain, 10 microM 17beta-oestradiol produced significantly (P < 0.05) lower stimulation of G-proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17beta-Oestradiol, genistein and daidzein revealed a selective effect on various G-proteins (G(alphas), G(alpha o), G(alpha i1) or G(alpha 11) plus G(beta 1 gamma 2)) expressed in Sf9 cells. At a concentration of 10 microM, 17beta-oestradiol suppressed the H(2)O(2) and homocysteine stimulated G-proteins in the frontocortical membranes of control women to a greater extent than phytoestrogens. In AD, the suppressing effect of each compound was lower than in the controls. In the cell-free systems, micromolar concentrations of phytoestrogens scavenged OH(*) and the 2.2-diphenyl-1-picrylhydrazyl free radical (DPPH(*)) more than 17beta-oestradiol did. In the frontocortical membranes of control women, the 20 microM 17beta-oestradiol stimulated adenylate cyclase with 20% maximal effect, whereas, in AD, the effect was insignificant. Genistein did not stimulate enzyme either in control or AD frontocortical membranes. Our data confirm that the agents stimulate G-proteins in control and AD women's brains, although 17beta-oestradiol and phytoestrogens have similarities and differences in this respect. We suggest that, besides the ER-dependent one, the ER-independent antioxidant mechanism is responsible for the oestrogen stimulation of G-proteins in the brain membranes. Both of these mechanisms could be involved in the neuroprotective signalling of oestrogens that contributes to their preventive/therapeutic action against postmenopausal neurological disorders.

Homocysteine status in former top-level male athletes: possible effect of physical activity and physical fitness.

The importance of elevated homocysteine (Hcy) as a risk marker for cardiovascular disease is continuously under debate. Lifestyle factors may increase the total Hcy (tHcy) level of the plasma, but there are no consistent findings relating to Hcy, physical activity, and cardiorespiratory fitness. Cross-sectional measurement from an ongoing follow-up study was performed on 77 former male athletes and 33 sedentary controls (age range 35-62 years). Lifestyle parameters (current physical activity patterns, smoking, etc.), anthropometric and blood pressure data, and data about tHcy, reduced, and oxidized glutathione (GSH, GSSG, respectively) in blood, lipoproteins, and maximal oxygen consumption (VO(2max)) were collected. Our study results showed that the subgroup of physically active ex-athletes (n=52) had a significantly lower tHcy level and glutathione redox ratio (GSSG:GSH) in comparison with the subgroup of sedentary ex-athletes (n=25). tHcy level was inversely related to cardiorespiratory fitness (VO(2max)/kg). Dietary and smoking habits were not significantly associated with the tHcy level in our study group. In conclusion, the research findings indicate that both current physical activity and cardiorespiratory fitness are significantly inversely associated with an elevated homocysteine level in middle-aged former athletes.

Pre-treatment with hyperoxia before coronary artery bypass grafting - effects on myocardial injury and inflammatory response.

BACKGROUND: In experimental studies, exposure to hyperoxia for a limited time before ischaemia induces a low-grade systemic oxidative stress and evokes an (ischaemic) preconditioning-like effect of the myocardium. We hypothesised that hyperoxia before cardioplegia could protect the myocardium against necrosis and stunning caused by ischaemia-reperfusion. METHODS: Forty patients undergoing coronary artery bypass grafting were randomly exposed to an oxygen fraction of 0.4 or > 0.96 in inspired air on an average of 120 min before cardioplegia. Blood for troponin I, creatine kinase-MB, lactate, glutathione and interleukin-6 was sampled from arterial and coronary sinus cannulae during 20 min of reperfusion. Additional arterial samples were drawn 60 min after declamping and in the first post-operative morning. The cardiac index and right and left ventricular stroke work indices were measured before sternotomy and up to 12 h post-operatively. RESULTS: Troponin I, creatine kinase-MB and lactate did not differ between the groups. Hyperoxic pre-treatment had no impact on the post-operative haemodynamic indices measured with the thermodilution pulmonary artery catheter. More oxidised glutathione was released in the hyperoxia group in the first minute of reperfusion (P = 0.015). Hyperoxic pre-treatment abolished the myocardial release of interleukin-6 during 20 min of reperfusion (P = 0.021 vs. controls). In the first post-operative morning, interleukin-6 was higher in the hyperoxia group [127.0 (86.0-140.0) vs. 85.2 pg/ml (66.6-94.5 pg/ml); P = 0.016]. CONCLUSIONS: Exposure to >96% oxygen before cardioplegia did not attenuate ischaemia-reperfusion injury of the heart in patients undergoing coronary artery bypass grafting. The only potentially beneficial effect observed was the decreased transmyocardial release of interleukin-6.

Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects.

Arterial stiffening may be linked to the reduced bioactivity of nitric oxide (NO) and increased plasma concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). The aim of this study was to investigate whether large (C1) and small artery (C2) elasticity is associated with endothelial function index (EFI) and plasma concentration of ADMA. We included 63 healthy subjects, aged 19 to 70 years, in the study. EFI, C1 and C2 were assessed by pulse wave analysis (PWA) and ADMA level was measured using an enzyme-linked immunoassay. Linear regression analysis revealed significant positive correlation between EFI and both C1 and C2 (R = 0.29, p = 0.02; R = 0.38, p = 0.002, respectively). A significant inverse association occurred between ADMA and C1 as well as C2 (R = -0.32, p = 0.03; R = -0.37, p = 0.009, respectively). In multiple regression analysis, C2 was determined by EFI, ADMA, age and BMI, and C1 was correlated with EFI, age and BMI. These findings suggest that endothelial vasodilatory dysfunction and accumulation of ADMA may be important mechanisms underlying reduced arterial elasticity in healthy subjects.

Atherogenic inflammatory and oxidative stress markers in relation to overweight values in male former athletes.

OBJECTIVE: To evaluate inflammation- and oxidative stress-related (OxS) background in former athletes in relation to overweight and abdominal obesity status. DESIGN: Cross-sectional data from ongoing follow-up study. SUBJECTS: A total of 60 middle-aged former athletes (46.6+/-7.5 years; 181.1+/-7.2 cm; 88.1 +/- 12.9 kg) and 54 age-matched controls (48.1+/-7.3 years; 181.4 +/- 6.2 cm; 89.7 +/- 14.4 kg). MEASUREMENTS: Anthropometric characteristics, serum lipoproteins (CHOL, HDL-C, LDL-C, TG), oxidized LDL (oxLDL), diene conjugates (DC) and high-sensitive C-reactive protein (hsCRP). Information about the physical activity and other lifestyle variables were collected by the questionnaire. RESULTS: Ex-athletes were characterized by significantly higher physical activity characteristics and lower CHOL and oxLDL in comparison with controls. Correlation analysis among ex-athletes revealed negative associations between all measured overweight data (body mass index, fat percentage, waist to hip circumferences and waist circumference (WC)), and current physical activity. Current physical activity was significantly related to OxS and inflammatory characteristics (oxLDL, DC and hsCRP) among the ex-athletes, but not among the control group. The most expressed positive correlations were found between WC, hsCRP, triglycerides (TG), DC and oxLDL in both study groups. CONCLUSION: Our study results suggest that there exists an independent (adjusted for potential confounders) association between overweight, abdominal obesity, and atherogenic inflammatory and oxidative stress markers in ex-athletes as well as in age-matched controls. Major findings of our study show that WC is the best correlate of hsCRP, oxLDL, DC and TG levels.

Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort.

BACKGROUND: Whether hepatitis B (HBV) coinfection affects outcome in HIV-1-infected patients remains unclear. OBJECTIVE: To assess the prevalence of HBV (assessed as HBsAg) coinfection and its possible impact on progression to AIDS, all-cause deaths, liver-related deaths and response to highly active antiretroviral therapy (HAART) in the EuroSIDA cohort. METHODS: Data on 9802 patients in 72 European HIV centres were analysed. Incidence rates of AIDS, global mortality and liver-related mortality, time to 25% CD4 cell count increase and time to viral load < 400 copies/ml after starting HAART were calculated and compared between HBsAg-positive and HBsAg-negative patients. RESULTS: HBsAg was found in 498 (8.7%) patients. The incidence of new AIDS diagnosis was similar in HBsAg-positive and HBsAg-negative patients (3.3 and 3.4/100 person-years, respectively) even after adjustment for potential confounders: the incidence rate ratio (IRR) was 0.94 [95% confidence interval (CI), 0.74-1.19; P = 0.61]. The incidences of all-cause and liver-related mortalities were significantly higher in HBsAg-positive subjects (3.7 and 0.7/100 person-years, respectively) compared with HBsAg-negative subjects (2.6 and 0.2/100 person-years, respectively). The adjusted IRR values were 1.53 for global (95% CI, 1.23-1.90; P = 0.0001) and 3.58 for liver-related (95% CI, 2.09-6.16; P < 0.0001) mortality. HBsAg status did not influence viral or immunological responses among the 1679 patients starting HAART. CONCLUSIONS: The prevalence of HBV coinfection was 9% in the EuroSIDA cohort. Chronic HBV infection significantly increased liver-related mortality in HIV-1-infected patients but did not impact on progression to AIDS or on viral and immunological responses to HAART.

High-sensitive C-reactive protein level and oxidative stress-related status in former athletes in relation to traditional cardiovascular risk factors.

OBJECTIVE: To analyze systemic and cellular oxidative stress-related indices as well as C-reactive protein level in former top-level athletes in relation to traditional cardiovascular risk factors. METHODS: A cross-sectional study was performed in 53 former male athletes and 25 sedentary controls (age range: 39-59 years). We measured anthropometric factors (BMI, fat percentage, WHR), resting blood pressure (SBP, DBP), serum cholesterol (CHOL), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), total antioxidant status (TAS), oxidized LDL-C (oxLDL), diene conjugates (DC), glutathione redox status, high-sensitive C-reactive protein (hsCRP), and leisure-time physical activity. RESULTS: Physically active former athletes had significantly lower mean overweight (BMI, fat percentage, WHR), better spectrum of atherogenesis indicators (CHOL, HDL-C, TG, TG:HDL-C ratio) and lower oxidative stress (oxLDL, oxLDL:LDL-C ratio, DC) values than sedentary ex-athletes. No significant differences in these variables were found between the sedentary ex-athletes and control group. Significant associations were found between physical activity (METs), SBP, DBP, hypertension, CHOL, HDL-C, TG, TG:HDL-C ratio, oxLDL, oxLDL:LDL-C ratio, DC and hsCRP. CONCLUSIONS: A physically active lifestyle is related to a lower cardiovascular disease (CVD) risk profile including a substantially lower systemic and cellular oxidative stress status as well as C-reactive protein level in middle-aged men.

Is elective abdominal aortic aneurysm repair accompanied by high grade oxidative stress?

BACKGROUND AND AIMS: During elective abdominal aortic aneurysm repair (AAAR), lower torso ischaemia-reperfusion event is unavoidable. Previous studies on AAAR have reported the importance of oxidative stress (OS) in ischaemia-reperfusion injury, however, the grade of OS has not been adequately clarified up to now. The aim of this study was to perform a complex investigation of the time-course and grade of systemic and cellular OS in patients undergoing AAAR. MATERIAL AND METHODS: Arterial blood samples were taken from 18 patients undergoing elective AAAR (at four points in time: before anaesthesia, 5 min after aortic clamping and 5 min and 30 min after clamp removal). Diene conjugates (DC), thiobarbituric acid reactive substances (TBARS), total antioxidative capacity (TAC), glutathione redox ratio (GSSG/GSH), and levels of antioxidative enzymes as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) were measured from the radial arterial blood. RESULTS: 30 min after the removal of the aortic cross-clamp, arterial CAT showed significant elevation (96.0 vs 56.9 U/l, p < 0.05); GSHPx was significantly elevated (51.5 vs 39.9 U/g Hgb, p < 0.05) and TAC was decreased (31.4 vs 36.5%, p < 0.05) in comparison with preoperative value. CONCLUSIONS: We found limited alterations of several OS parameters, which do not characterize either systemic or cellular high-grade OS during elective AAAR.

Oxidative stress markers in pre-uremic patients.

AIM: The present study was designed to investigate a complex of oxidative stress (OS) markers in patients with chronic renal failure (CRF) and to study the relationship between different OS markers and degree of renal failure. The following indices of OS were measured in plasma: oxidized glutathione (GSSG), reduced glutathione (GSH), total glutathione (TGSH), glutathione redox ratio (GSSG/GSH) and resistance of lipoprotein fraction to oxidation (lag phase of LPF). Baseline diene conjugation level of lipoprotein fraction (BDC-LPF), total antioxidative activity (TAA), diene conjugates (DC), lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS) were measured in serum. All markers in plasma and serum were measured both in patients with CRF and in healthy controls. SUBJECTS AND METHODS: Blood samples were obtained from 38 patients with CRF and from 61 healthy controls. Routine biochemical analyses were performed by using commercially available kits. RESULTS: Levels of DC, BDC-LPF, LOOH, GSSG and GSSG/GSH ratio were significantly increased and lag phase of LPF was significantly shortened in patients with CRF compared with healthy controls. Serum creatinine and urea levels correlated significantly with GSSG level and GSSG/GSH in patients with CRF. A significant inverse correlation was found between glutathione redox ratio and lag phase of LPF and between GSSG level and BDC-LPF. CONCLUSIONS: The findings suggest that renal patients are in a state of oxidative stress compared with healthy controls. The most informative indices to evaluate the degree of OS in CRF were: GSSG level, GSSG/GSH status, lag phase of LPF and BDC-LPF.

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.

The cerebrocortical areas in normal brain aging and in Alzheimer's disease: noticeable differences in the lipid peroxidation level and in antioxidant defense.

The markers of oxidative stress were measured in four cerebrocortical regions of Alzheimer's disease (AD) and age-matched control brains. In controls the levels of diene conjugates (DC) and lipid peroxides (LOOH) were significantly higher in the sensory postcentral and occipital primary cortex than in the temporal inferior or frontal inferior cortex. The antioxidant capacity (AOC) was highest in the temporal, and GSH in the frontal inferior cortex. The highest activity of superoxide dismutase (SOD) and catalase (CAT) was found in the occipital primary cortex. Compared with controls, significantly higher level of DC and LOOH and attenuated AOC were evident in AD temporal inferior cortex. In AD frontal inferior cortex moderate increase in LOOH was associated with positive correlation between SOD activity and counts of senile plaques. Our data suggest that in AD cerebral cortex, the oxidative stress is expressed in the reducing sequence: temporal inferior cortex > frontal inferior cortex > sensory postcentral cortex approximately = occipital primary cortex, corresponding to the histopathological spreading of AD from the associative to primary cortical areas.

Acute immune response in respect to exercise-induced oxidative stress.

The relationship between exhaustive exercise, oxidative stress, the protective capacity of the antioxidant defense system and cellular immune response has been determined. Exhaustive exercise in well-trained young men (n=19)-induced leukocytosis, decreased proportion of activated-lymphocyte subsets (CD4+ and CD8+) expressing CD69, decreased lymphocyte mitogenic response to concanavalin A (ConA) and phytohemagglutinin (PHA), increased lipid peroxidation, increased total antioxidant status (TAS) and catalase activity, immediately after exercise. Suppressed blood concentration of T-lymphocyte subsets (CD3+, CD4+, CD8+, NK), increased TAS and blood total glutathione (TGSH) in early recovery period (30 min after exercise) were found. Strong positive correlation was observed between TGSH and lymphocyte mitogenic response to ConA and PHA (r=0.85 and 0.85, respectively) immediately after exercise. Moderate positive correlation was observed between TAS and lymphocyte mitogenic response to PHA (r=0.59) immediately after exercise as well as between TAS and lymphocyte mitogenic response to PHA and ConA (r=0.69 and 0.54, respectively). Moderate to weak correlation was observed between TAS and conjugated dienes with exercise (r=0.66) as well as in 30-min recovery (r=0.50). After a short-term bout of exhaustive exercise, immune system was characterized by acute phase response, which was accompanied with oxidative stress. Suppression of the cellular immunity 30 min after exercise shows that this period is not enough for recovery after exhaustive exercise. The results suggest the interactions between exercise-induced oxidative stress and immune response.