Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin.

To assess the consequences of oxidative stress in allergic and irritant contact dermatitis, we compared the iron level, unsaturated iron-binding capacity, total iron binding capacity, the percentage saturation of iron-binding capacity, the amount of diene conjugates as well as the amounts of total glutathione, reduced glutathione, oxidized glutathione, and the oxidized glutathione/reduced glutathione ratio in skin homogenate from lesional and nonlesional skin. Lesional skin samples were obtained from positive patch test sites to 5% NiSO4 in five subjects, and from chronic contact dermatitis lesions on the hands, which had exacerbated over 3--9 wk in six subjects. Contact dermatitis caused at least a 4-fold increase in the iron level in the lesional skin area compared with the nonlesional skin area (p < 0.02). The increase in the iron level depended on the duration of contact dermatitis and was accompanied by high unsaturated iron-binding capacity and total iron-binding capacity values in the positive patch test sites (p < 0.05), and by a high percentage saturation value in the chronic contact dermatitis lesions (p < 0.05). We found high indices for iron, total iron-binding capacity and diene conjugates in the apparently healthy skin of the patients with persistent contact dermatitis that significantly (p < 0.05) exceeded the corresponding values in the patients with only patch test reactions. In summary, we have succeeded in providing evidence that generalized oxidative damage of the skin occurs as a consequence of contact dermatitis in a restricted area.     

Lead-induced excessive lipid peroxidation and changes in local cerebral blood flow in rabbit brain

Lead-poisoning is a disease of environmental origin. The primary target for lead is the nervous system. Lead ions are able to accelerate lipid peroxidation (LP) and, hence, induce cellular damage. Endothelial cell alteration and cerebral microvessel dysfunction are important in lead-induced encephalopathy. It is possibile that the altered functional state of brain microvasculature cannot ensure the adequate level of local cerebral blood flow (LCBF). The purpose of the present study was to evaluate LP in brain tissue homogenates of the cerebral cortex (CTX) and hypothalamus (HYP) of 15 lead-exposed vs seven control rabbits after a short-time lead exposure (5 and 10 days, 40 mg/kg). Another aim was to compare the dynamics of changes in LP and LCBF, detected by the H₂ clearance method in another group (seven lead-exposed rabbits vs seven controls). The basal level of thiobarbituric acid reactive substances (TBARS), the Fe-stimulated part of the TBARS (Fe-TBARS) and diene conjugates (DC) were used for the evaluation of LP in the brain tissue. A tendency to the slight enhancement of TBARS and DC concentrations in brain homogenates 5 days after the 10 days lead exposure period was found (CTX p < 0.05). The enhancement of the Fe TBARS was expressed maximally on 1 day after 10 day exposure period (CTX p < 0.05, HYP p < 0.001 compared to controls). The biphasic reaction of changes in LCBF was detected: during (5th day) and in 1 day after a 10 day exposure period a decrease of LCBF in both investigated regions was found (10.5 and 9.3 ml/100g/min i.e. 28.6 and 24.1%, respectively, in CTX, p < 0.05; and 11.2 and 10.1 ml/100g/min i.e. 19.9 and 18.7%, respectively in HYP, p < 0.05); on the 5th day after exposure minimal tendency to increase was found (7.1 ml/100g/min, p < 0.01 in HYP compared with controls). In conclusion, lead induces excessive LP in brain homogenates and disturbances in LCBF. However, the causal relationship between those events remains to be proven.     

HIV-1 subtypes and response to combination antiretroviral therapy in Europe

BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western Europe/North America on the basis of the most prevalent subtype, B. However, non-B subtypes are increasingly spreading worldwide. OBJECTIVE: To compare virological and immunological response to cART between patients infected with B and non-B subtypes across Europe. DESIGN: EuroSIDA prospective, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6-12 months after starting cART. A virological response was defined as a viral load <500 copies/mi and immunological response as a CD4+ T-cell count increase of > or =100 cells/mm(3). RESULTS: Forty-five percent of patients were antiretroviral naive at initiation of cART. Virological suppression was achieved by 58% of 689 subtype-B-infected patients and 66% of 102 non-B-infected patients (P=0.159). After adjustment for potential confounders, there was no significant difference in odds of achieving virological suppression (non-B compared with B; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.58-1.93, P=0.866). An immunological response was achieved by 43% of 753 B-infected patients and 48% of 114 non-B-infected patients (P=0.334). After adjustment, there was no significant difference in odds of an immunological response (OR: 1.17, 95% CI: 0.73-1.87, P=0.524). CONCLUSIONS: There was no evidence of significant differences in virological or immunological response to cART between patients infected with HIV-1 B and non-B subtypes.     

Impact of oxidative stress on arterial elasticity in patients with atherosclerosis

BACKGROUND: Alterations in the elastic behavior of arteries is an early sign of vascular damage in atherogenesis and may be promoted by oxidative stress (OxS). However, studies designed for simultaneous assessment of arterial elasticity and OxS status in patients with peripheral arterial disease (PAD) are absent. The purpose of this study was to assess large (C1) and small artery elasticity (C2) and indices of OxS in patients with PAD as well as to investigate possible relationships between these parameters. METHODS: Arterial elasticity was assessed noninvasively by pulse wave analysis (PWA) and biochemical measurements were taken from 38 patients with PAD and from 28 matched control subjects. The elasticity indices of the arteries were derived from PWA based on the modified Windkessel model and the OxS status was measured using urinary 8-iso-prostaglandin F2alpha (F2-IsoPs) and plasma baseline diene conjugates of low-density lipoproteins (LDL-BDC). RESULTS: Patients with PAD showed significantly reduced C1 and C2 and increased values of F2-IsoPs and LDL-BDC. There was an inverse association between C1 and F2-IsoPs, as well as between C2 and F2-IsoPs (R=-.3, P=.04; R=-.49, P=.002, respectively) in the patient group, but not in the controls. After controlling for potential confounders in a multiple regression model, the associations between C2 and F2-IsoPs remained significant in the patient group (P<.001). CONCLUSIONS: The possible link between arterial elasticity and F2-IsoPs in patients with PAD suggests that oxidative modifications may be involved in alterations of arterial elastic properties in atherosclerosis.     

Association between arterial elasticity, C-reactive protein and maximal oxygen consumption in well-trained cadets during three days extreme physical load: a pilot study

Regular aerobic training has beneficial effects on inflammatory pathways and on arterial elasticity, which are both important cardiovascular risk factors. The aim of the present study was to evaluate the effect of extreme physical load on arterial elasticity and inflammatory markers in well-trained healthy men who participated in a high-ranking combat course. Seven well-trained male cadets were examined during an international military combat course of 3.5 days duration. Small (C2) and large (C1) artery elasticity was assessed using diastolic pulse wave analysis. Inflammatory markers and arterial elasticity measurement were performed before and after the competition. The extreme prolonged physical load caused individually different responses in arterial elasticity, C-reactive protein (CRP) and creatine kinase in individual cadets. Maximal oxygen consumption (VO(2) max kg(-1)) correlated significantly with the change (Delta-difference between baseline and 24 h recovery period) of creatine kinase (r= -0.78; p=0.04) and DeltaC2 (r=0.78; p=0.04) and DeltaC1 (r=0.82; p=0.02). In multivariate analysis (R(2)=0.89, p=0.01) the DeltaC2 correlated strongly with VO(2) max kg(-1) (p=0.005) and with the DeltaCRP (p=0.03), whereas the DeltaC1 correlated only with VO(2) max kg(-1) and did not correlate significantly with the DeltaCRP. Changes in small arterial elasticity induced by extreme physical load were significantly related to VO(2) max kg(-1) and DeltaCRP, whereas the change of large artery elasticity was only associated with VO(2) max kg(-1). Our preliminary results indicate that acute exercise-induced inflammation may affect small artery elasticity. However, further, more extensive studies are needed in this area.     

Early postoperative function of the heart after coronary artery bypass grafting is not predicted by myocardial necrosis and glutathione-associated oxidative stress

BACKGROUND: To investigate whether cardioplegia-related myocardial necrosis, lactate and glutathione release are predictive for early postoperative cardiac function after coronary artery bypass grafting (CABG). METHODS: Twelve patients with stabile angina scheduled for elective CABG were included. Myocardial release of troponin I (Tn I), creatine kinase MB isoenzyme mass (CK-MB), oxidized glutathione (GSSG) and lactate in blood were measured before cardioplegia, and up to 20 min thereafter. Cardiac function was assessed for 12 postoperative hours. RESULTS: Release of Tn I and CK-MB peaked at 20 min (-14.5+/-24.1 ng/ml and -23.9+/-30.6 ng/ml, respectively) and lactate at 1 min of reperfusion (-1.5+/-0.6 mmol/l). Significant GSSG release occurred at 5 min, with concomitant increase of glutathione redox ratio. The changes were not correlated to ischemic time. Cardiac index was increased after CPB and remained higher than preoperative value until the first postoperative morning. No correlations between postcardioplegic heart function and markers of tissue injury were found. CONCLUSIONS: The extent of myocardial reversible and irreversible injury does not predict early postoperative contractile function of the heart.     

Antioxidative probiotic fermented goats' milk decreases oxidative stress-mediated atherogenicity in human subjects

The increasing interest in a healthy diet is stimulating innovative development of novel scientific products in the food industry. The viable lactic acid bacteria in fermented milk products, such as yoghurt, have been associated with increased lactose tolerance, a well-balanced intestinal microflora, antimicrobial activity, stimulation of the immune system and antitumoural, anticholesterolaemic and antioxidative properties in human subjects. Recently, we have studied a human Lactobacillus spp. strain that possesses antioxidative activity. The aim of the present pilot study was to develop goats' milk fermented with the human antioxidative lactobacilli strain, Lactobacillus fermentum ME-3, and to test the effect of the fermented probiotic goats' milk on oxidative stress markers (including markers for atherosclerosis) in human blood and urine and on the gut microflora. Twenty-one healthy subjects were assigned to two treatment groups: goats' milk group and fermented goats' milk group (150 g/d) for a period of 21 d. Consumption of fermented goats' milk improved anti-atherogenicity in healthy subjects: it prolonged resistance of the lipoprotein fraction to oxidation, lowered levels of peroxidized lipoproteins, oxidized LDL, 8-isoprostanes and glutathione redox ratio, and enhanced total antioxidative activity. The consumption of fermented goats' milk also altered both the prevalence and proportion of lactic acid bacteria species in the gut microflora of the subjects. We conclude that the goats' milk fermented with our special antioxidative lactobacilli strain Lactobacillus fermentum ME-3 exhibits anti-atherogenic effects.     

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.     

Characterization of the antioxidant profile of human saliva in peri-implant health and disease

OBJECTIVES: Peri-implant disease is considered to be an inflammatory disease, but many aspects of its pathogenesis remain unknown. At present, peri-implant disease is considered to be initiated and perpetuated by a small group of predominantly Gram-negative, anaerobic, or micro-aerophilic bacteria that colonize the subgingival area. Bacteria cause the observed tissue destruction directly by toxic products and indirectly by activating host defence systems, i.e. inflammation. A variety of molecular species appears in the inflamed tissues, among them are reactive species such as free radicals and reactive oxygen species (ROS). The purpose of this study was to assess levels of various antioxidants in saliva to identify differences between the saliva of patients with healthy peri-implant tissues and patients with peri-implant disease, and to examine whether the whole saliva of those with peri-implant disease conditions might have lower levels of antioxidants than that of healthy individuals. MATERIALS AND METHODS: Thirty healthy adult volunteers (14 men and 16 women) with implant-supported overdentures (Ankylos Biofunctional Implants) were selected from the group of patients from Tallinn Dental Clinic. Biochemical and clinical parameters evaluated were the following ones: the levels of urate, ascorbate, myeloperoxidase in saliva, total antioxidant status of saliva, pocket probing depth (mm), gingival index (0, 1, 2, or 3), and bleeding on probing (0 or 1). RESULTS AND CONCLUSION: Total antioxidant status (TAS) of saliva and concentration of uric acid and ascorbate, which are the main salivary antioxidants, are significantly decreased in patients with peri-implant disease. TAS in healthy subjects was 0.41+/-0.10 for resting saliva and 0.31+/-0.09 for stimulated saliva; in diseased subjects TAS was 0.19+/-0.07 and 0.12+/-0.03, respectively. In healthy subjects, the concentration of urate was 307.2+/-78.06 microM/l in resting saliva and 241.5+/-89.09 microM/l in stimulated saliva. In diseased patients, the concentration of urate was 120+/-36.13 and 91.60+/-39.35 microM/l, respectively. The concentration of ascorbate did not differ in resting and stimulated saliva. In healthy subjects, it was 2.79+/-0.81 mg/l and in diseased subjects, it was 1.54+/-0.30 mg/l. This may indicate that excessive ROS production in peri-implant disease is leading to the situation of excessive oxidative stress, which may be an important factor contributing the destruction of peri-implant tissues. The importance of these findings may be the better understanding of the processes involved in the pathogenesis of peri-implant disease and that the treatment of peri-implant disease may involve adjuvant anti-oxidants supplementation together with cumulative interceptive supportive therapy concept introduced by Mombelli & Lang.