Reduced extracellular phagocyte oxidative activity, antioxidant level changes and increased oxidative damage in healthy human blood as a function of age

Age-related changes in the blood antioxidant status, in the prooxidative activity of peripheral phagocytes and in the markers of oxidative injury were simultaneously examined in the circulation of 45 middle-aged and elderly healthy volunteers. The results showed a decrease in the opsonin-dependent and -independent extracellular-phagocyte oxidative activity, evaluated by means of luminol chemiluminescence. An increase in the portion of the mitochondrial superoxide generation within the total oxidative phagocyte response was evaluated by means of lucigenin chemiluminescence. The erythrocyte copper/zinc superoxide dismutase increased with age, while blood catalase and glutathione peroxidase activities remained unchanged. The levels of blood SH-groups decreased with age. An age-related increase in blood concentration of thiobarbituric acid-reactive material, a marker of oxidative damage, was detected. Some data, illustrating the existence of a delicate balance between oxidants and prooxidants, were also obtained. Further studies on the interrelationship between the components determining pro/antioxidative status in an organism may prove useful for developing a complex strategy in combating ageing.     

The Interaction of Copper (Cu++) with the Erythrocyte Membrane and 2,3-Dimercaptopropanesulphonate in Vitro: A Source of Activated Oxygen Species

Abstract: The therapy of copper poisoning and of Wilson's disease with 2,3-dimercaptopropane-1-sulphonate (DMPS) may increase the copper-induced haemolysis. Some aspects of the mechanism of this effect were investigated. The possible generation of activated oxygen species during the interaction of Cu⁺⁺ and DMPS was studied using a chemiluminescent method detecting oxygen radicals. It was found that incubation of DMPS with copper ions (free or bond with erythrocyte membranes) is accompanied with generation of oxygen radicals. Activated oxygen species produced via O₂^- are able to increase the haemolytic effects of cupric salts. Hence DMPS treatment in cases of copper poisonings or Wilson's disease may involve risk of side effects on the basis of activated oxygen species generation.     

Dynamics of free radical processes in acute ischemic stroke: influence on neurological status and outcome.

The dynamics of free radical processes during the acute stage of ischemic stroke and their relationship with the clinical status of patients were studied. An enhanced extracellular generation of reactive oxygen species (ROS) by peripheral phagocytes was observed in severe stroke patients during the whole acute stage. This generation correlated positively with the size of infarct, the severity of neurological deficit and handicap and correlated negatively with the improvement of the neurological status of patients. An increase in the activity of two enzymes from the antioxidant defense mechanism, catalase and glutathione peroxidase, was registered during the whole acute phase of stroke, regardless of its severity. The concentration of lipid peroxidation products increased over time. Blood concentration of thiobarbituric acid-reactive material (TBARM) correlated positively with the size of infarct, the severity of neurological deficit and handicap. In conclusion, extracellular ROS generation by phagocytes and blood TBARM concentration could be used as indicators for stroke outcome.     

Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging

In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI‐based grading of the tibial cartilage was also compared with a ‘macroscopic’ grading based on direct visual inspection of dissected joints. The test–retest precision for MRI‐based measurement was ≤6.4%. MRI‐based measurements correlated well with volumes of surgically resected cartilage (r = 0.97, pair‐wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non‐operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP‐treated group than in the non‐treated group. Copyright © 2011 John Wiley & Sons, Ltd.     

Motor Evoked Potentials Improve Targeting in Deep Brain Stimulation Surgery

ObjectivesOne of the main challenges posed by the surgical deep brain stimulation (DBS) procedure is the successful targeting of the structures of interest and avoidance of side effects, especially in asleep surgery. Here, intraoperative motor evoked potentials (MEPs) might serve as tool to identify the pyramidal tract. We hypothesized that intraoperative MEPs are useful to define the distance to the pyramidal tract and reduce the occurrence of postoperative capsular side effects.Materials and MethodsMotor potentials were evoked through both microelectrode and DBS-electrode stimulation during stereotactic DBS surgery on 25 subthalamic nuclei and 3 ventral intermediate thalamic nuclei. Internal capsule proximity was calculated for contacts on microelectrode trajectories, as well as for DBS-electrodes, and correlated with the corresponding MEP thresholds. Moreover, the predictivity of intraoperative MEP thresholds on the probability of postoperative capsular side effects was calculated.ResultsIntraoperative MEPs thresholds correlated significantly with internal capsule proximity, regardless of the stimulation source. Furthermore, MEPs thresholds were highly accurate to exclude the occurrence of postoperative capsular side effects.ConclusionsIntraoperative MEPs provide additional targeting guidance, especially in asleep DBS surgery, where clinical value of microelectrode recordings and test stimulation may be limited. As this technique can exclude future capsular side effects, it can directly be translated into clinical practice.     

Risk Factors for Surgery in Pediatric Patients with Crohn's Disease

ObjectivePediatric Crohn''s disease (CD) has a more aggressive phenotype and course than in adults. Many patients develop complications that require surgery. The aim of this study was to identify the factors associated with increased risk for surgical intervention in pediatric patients with CD.Subjects and MethodsThis study is a retrospective review of medical records. We analyzed the following variables: sex, age at diagnosis, presenting symptoms, duration of symptoms before diagnosis, disease location and severity, the presence of extraintestinal manifestations, and the presence of anti-Saccharomyces cerevisiae antibodies. Univariate analysis using the Mann-Whitney test and Fisher''s exact test was performed to detect the factors associated with surgery. Potential risk factors with p < 0.05 were further analyzed using a multivariate binary logistic regression model.ResultsFifty-seven patients (27 girls and 30 boys) were included in the analysis. More than one-fourth of them (28.1%) required surgical management. Female sex (p = 0.043), disease behavior (p = 0.012), and the presence of perianal disease at diagnosis (p < 0.001) were the variables associated with surgical intervention. Stricturing disease (B2) (odds ratio [OR], 24.944; p = 0.016), stricturing and penetrating disease (B2B3) (OR, 28.276; p = 0.011), and the presence of perianal disease at diagnosis (OR, 95.802; p = 0.001) were independent risk factors for surgery. Female sex was associated with surgery without being an independent risk factor.ConclusionFemales with B2 or B2B3 or the presence of perianal disease at diagnosis are at a higher risk for surgery and should be considered for more aggressive medical treatments.