Allergic contact dermatitis is accompanied by severe abnormal changes in antioxidativity of blood.

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

Recurrent ulceration after proximal gastric vagotomy. Possible role of mucosal barrier

Between 1971 and 1986 532 proximal gastric vagotomies were carried out at the Pelgulinna Hospital. The five-year recurrence rate was 5.5% (n = 29). We have studied 40 patients with chronic duodenal ulceration, 20 patients who had effective proximal gastric vagotomy, and seven patients who presented with recurrent ulcers after proximal gastric vagotomy. Patients who had positive Hollander tests after vagotomy, and those with disorders of gastric motility, were excluded. In the group with recurrent ulcers the concentration of neutral mucopolysaccharides in the gastric juice was significantly lower than in the other two groups, and it correlated with the amount of material showing a positive reaction to periodic acid Schiff (PAS) in the gastric mucosa. This group also had significantly higher mean serum gastrin concentrations and mast cell degranulation rates in the mucosa of the fundus and the antrum. We conclude that qualitative changes in the production of gastric mucus lead to defective functioning of the mucosal barrier in patients with recurrent ulcers and may be one of the causes of recurrences.     

Metabolic factors and oxidative stress in osteoarthritis: a case–control study

Previous studies suggest that metabolic disturbances might be involved in the development of osteoarthritis (OA). Associations have been found between the individual components of metabolic syndrome (MetS) and OA. MetS has been associated with increased oxidative stress (OxS). The study aimed to clarify the role of MetS components in OA and to evaluate the levels of OxS in OA patients and in age-matched controls. Fifty-five patients with end-stage OA (age 63?±?7 years) prior to hip or knee joint replacement surgery and 55 age-, gender- and body mass index matched controls (61?±?8 years) were enrolled in the study. Serum levels of glucose, insulin, c-peptide, cholesterols and OxS markers were recorded. Homeostasis model assessment for insulin resistance was used as the proxy measure of insulin resistance. Radiographic severity was assessed using the Kellgren–Lawrence score. The OA patients had higher total peroxide concentration and oxidative stress index [488 (250–612) μmol/L vs. 326 (168–442) μmol/L, p?=?.011 and 34 (17–51) vs. 20 (11–28), p?=?.002, respectively] and decreased total antioxidant capacity (1.49?±?0.27 vs. 1.66?±?0.27?mmol trolox equivalent/L, p=?.008) compared with the controls. In addition, OA group had significantly higher level of C-peptide compared with the controls [1.8 (0.94–2.47) vs. 1.3 (0.46–1.42) ng/mL, p?<?.001, respectively]. Furthermore, OA radiographic severity was independently associated with LDL-cholesterol (p?=?.007) and oxidized LDL (p?=?.022). This study demonstrates that end-stage OA patients have increased levels of OxS and decreased antioxidant capacity. OA is associated with impaired lipid metabolism and dysglycemia. Our results underline the importance OxS and metabolic disturbances in the pathogenesis of OA.     

Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis

Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however, their causal relationship is not yet completely understood. Much attention has been given to the possibility that inflammation is a primary process of atherosclerosis and that OxS may be a by‐product of the inflammatory process. We hypothesized, accordingly, that chronic systemic inflammation affects endothelial vasomotor function in the subclinical condition, whereas oxidative modifications are more involved in the structural stiffening of the arteries in atherosclerosis. The aim of our study was to test this hypothesis. Endothelial function and arterial stiffness were assessed non‐invasively by pulse wave analysis, and blood/urinary samples were taken in 39 patients with peripheral arterial disease as well as in 34 controls. The patients showed significantly reduced endothelial function index (EFI) and increased augmentation index (AIx), as well as higher estimated aortic pulse wave velocity (PWV) and elevated values of the intercellular adhesion molecule‐1 (ICAM‐1), high sensitivity C‐reactive protein, myeloperoxidase and urinary 8‐iso‐prostaglandin F_2a (F₂‐IsoPs). There was an inverse association between EFI and ICAM‐1 (R = ?0.44, p = 0.009) in the controls, but not in the patients. Augmentation index and estimated aortic PWV correlated with F₂‐IsoPs only in the patients (R = 0.5, p = 0.001; R = ?0.43, p = 0.006, respectively). After controlling for potential confounders, these associations remained significant. The study demonstrates that impairment of endothelial vasomotor capacity is affected by degree of inflammation in the subclinical condition, whereas arterial stiffening is determined by level of oxidative modifications in atherosclerosis.     

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.     

Protective effect of antioxidants on pulmonary endothelial function after cardiopulmonary bypass

OBJECTIVES: Pulmonary endothelium-dependent vasodilation is impaired after cardiopulmonary bypass. One explanation might be the generation of reactive oxygen species during the period without flow in the pulmonary artery. The aim of the current study was to investigate if treatment with antioxidants could improve pulmonary endothelial function after cardiopulmonary bypass and influence the blood oxidative status. DESIGN: A prospective, randomized, double-blind study. SETTING: The operating room, intensive care unit, and the biochemistry laboratory in University Hospitals. PARTICIPANTS: Patients scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Treatment with vitamin E, vitamin C, allopurinol, and acetylcysteine (n = 12) or placebo (n = 10). MEASUREMENTS AND MAIN RESULTS: The pulmonary reactivity to an infusion of acetylcholine and markers of oxidative stress in blood were measured before and after cardiopulmonary bypass. Sixteen control patients received saline instead of acetylcholine. Before surgery the pulmonary vascular resistance index decreased during infusion of acetylcholine by 24% and 21% in the treatment and placebo groups. After surgery the decrease was 20% and 8%, respectively, (p = 0.422 and p = 0.026) compared with preoperative response. Pulmonary vasodilation induced by acetylcholine was better maintained in the group treated with antioxidants (p = 0.048). In the treatment group, the blood concentrations of early intermediates of lipid peroxidation were higher, but not that of the end products. Glutathione and oxidized glutathione increased after cardiopulmonary bypass in the treatment group. CONCLUSION: The better maintained endothelium-dependent vasodilation after cardiopulmonary bypass in the treatment group indicated that antioxidant therapy reduced endothelial dysfunction.     

Effects of stimulation of nitric oxide synthesis on large artery stiffness in patients with peripheral arterial disease

The role of endothelium-derived nitric oxide (NO) in modulation of large artery stiffness in patients with peripheral arterial disease (PAD) is unexplored. The aim of this study was to evaluate, using pulse wave analysis (PWA), changes in aortic and systemic arterial stiffness following administration of nitroglycerin and beta(2)-agonist salbutamol in PAD patients (n = 24) and in healthy controls (n = 24). Changes in estimated aortic pulse wave velocity (T(r)) and in augmentation index (AIx), following administration of nitroglycerin and salbutamol, were assessed using PWA. Salbutamol-induced changes in T(r) and in AIx were significantly reduced in PAD patients (P < 0.001 and < 0.001, respectively), while nitroglycerin-produced changes were not different (P = 0.25 and 0.35, respectively). Changes in T(r) after salbutamol administration were independent of changes in mean arterial pressure (MAP) (R = -0.21, P = 0.16). This study shows that stimulation of NO synthesis fails to modify stiffness of the large arteries in PAD patients and changes in aortic stiffness are independent of changes in MAP. Our data support the utility of PWA as a non-invasive method for assessment of NO-mediated vascular changes.     

Immunological, antioxidative, and morphological response in combined treatment of ofloxacin and Lactobacillus fermentum ME-3 probiotic in Salmonella Typhimurium murine model

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

Changes of plasma asymmetric dimethylarginine levels after coronary artery bypass grafting

OBJECTIVES: We investigated whether coronary artery bypass grafting affects plasma asymmetric dimethylarginine (ADMA) concentrations and whether precardioplegic hyperoxia influences ADMA release from the heart. DESIGN: Twenty two patients were randomized into control (n = 11) and hyperoxia (n = 11, ventilated with >96% oxygen before cardiopulmonary bypass) groups. Arterial and coronary sinus blood was sampled before cardioplegia and during early reperfusion. Arterial samples were drawn 60 min after declamping of the aorta, and on the first postoperative day. RESULTS: Baseline arterial values of ADMA were not different between groups (0.59+/-0.18 micro mol/l control, 0.63+/-0.13 micro mol/l hyperoxia group). Negligible release of ADMA into coronary sinus was detected 20 min after cardioplegia. A significant decrease of arterial ADMA was observed by the first postoperative morning (0.42+/-0.16 micro mol/l in control, and 0.38+/-0.07 in hyperoxia group, p < 0.01 compared to baseline). CONCLUSIONS: CABG with cardioplegia is associated with decrease of ADMA by the first postoperative morning. Reperfusion of cardioplegic heart did not result in significant release of ADMA. Pretreatment with hyperoxia had no influence on myocardial release and arterial levels of ADMA.