OBJECTIVEExtracorporeal circulation is associated with ischaemia-reperfusion-induced oxidative stress and atrial fibrillation (AF). Ageing is the major risk factor for this arrhythmia. Reinforcing the antioxidant defence system would be expected to protect the myocardium against ischaemia-reperfusion damage. We studied the effect of antioxidant reinforcement and ageing on the occurrence of postoperative AF.METHODSA randomized, double-blind, placebo-controlled trial was performed in patients scheduled for cardiac surgery with extracorporeal circulation. Supplementation with omega-3 polyunsaturated fatty acid (PUFA) and vitamins C and E, or placebo was administered to 152 patients divided by age: young patients (30-59 years) and old patients (60-80 years). For the detection of AF, we used 12-lead and Holter EKGs. Antioxidant enzyme activity was determined in atrial tissue. Oxidative stress was assessed through plasma malondialdehyde levels.RESULTSSupplemented patients over 60 years old showed higher glutathione peroxidase activity than control patients in the same age range. There was no difference between the supplemented and placebo groups in patients under 60 years old. The decrease in the incidence of postoperative AF in supplemented patients was more marked in the older patients than in the younger ones.CONCLUSIONSSince the antioxidant supplementation with n-3 PUFAs and vitamins C and E resulted in a more marked reduction of postoperative AF in older patients, it could be suggested that the efficacy of this therapy improves with ageing.

Postoperative atrial fibrillation (AF) is the most common arrhythmia following cardiac surgery with extracorporeal circulation. The pathogenesis of postoperative AF is multifactorial. Oxidative stress, caused by the unavoidable ischemia-reperfusion event occurring in this setting, is a major contributory factor. Reactive oxygen species (ROS)-derived effects could result in lipid peroxidation, protein carbonylation, or DNA oxidation of cardiac tissue, thus leading to functional and structural myocardial remodeling. The vulnerability of myocardial tissue to the oxidative challenge is also dependent on the activity of the antioxidant system. High ROS levels, overwhelming this system, should result in deleterious cellular effects, such as the induction of necrosis, apoptosis, or autophagy. Nevertheless, tissue exposure to low to moderate ROS levels could trigger a survival response with a trend to reinforce the antioxidant defense system. Administration of n-3 polyunsaturated fatty acids (PUFA), known to involve a moderate ROS production, is consistent with a diminished vulnerability to the development of postoperative AF. Accordingly, supplementation of n-3 PUFA successfully reduced the incidence of postoperative AF after coronary bypass grafting. This response is due to an up-regulation of antioxidant enzymes, as shown in experimental models. In turn, non-enzymatic antioxidant reinforcement through vitamin C administration prior to cardiac surgery has also reduced the postoperative AF incidence. Therefore, it should be expected that a mixed therapy result in an improvement of the cardioprotective effect by modulating both components of the antioxidant system. We present novel available evidence supporting the hypothesis of an effective prevention of postoperative AF including a two-step therapeutic strategy: n-3 PUFA followed by vitamin C supplementation to patients scheduled for cardiac surgery with extracorporeal circulation. The present study should encourage the design of clinical trials aimed to test the efficacy of this strategy to offer new therapeutic opportunities to patients challenged by ischemia-reperfusion events not solely in heart, but also in other organs such as kidney or liver in transplantation surgeries.

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

ABSTRACT: BACKGROUND: Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the USH2A gene account for 74-90% of the USH2 cases. METHODS: To identify the genetic cause of the disease and determine the frequency of USH2A mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing. RESULTS: As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and in vitro experiments, 37 variants (23 of them novel) were classified as pathogenic mutations. CONCLUSIONS: This report provide a wide spectrum of USH2A mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin.

Preeclampsia is a high-prevalence systemic pregnancy disorder associated with maternal and foetal mortality. Its pathogenesis is unknown, but it is thought that oxidative stress and endothelial dysfunction may play a fundamental role. Von Willebrand factor (vWF), a marker of endothelial cell injury, can be found in different cells and zones of the placenta. To determine the differential immunoexpression of vWF at different tissue types of preeclamptic placenta and endothelial dysfunction markers at maternal serum of preeclamptic pregnancies. A case-control study was performed on a population of pregnant women with preeclampsia (n = 14), and normal pregnancies (n = 8). Placental and blood plasma samples were withdrawn at delivery. Immunohistochemical vWF expression in the placental tissue was determined. Endothelial dysfunction was assessed through plasminogen activator inhibitor (PAI) 1 and 2 ratio and vWF concentration in maternal plasma. P values less than 0.05 were considered statistically significant. Preeclamptic women showed increased plasma PAI-1/PAI-2 ratio (P < 0.05). There was diminished placental vWF expression in syncytiotrophoblast and increased in the intervillous space of preeclamptic placentas (P < 0.05). No significant differences in vWF expression were found in the villous endothelium and stroma, but it was significantly higher in maternal plasma (P < 0.05). In preeclampsia occurs endothelial damage and placental cell injury. Cell damage in syncytiotrophoblast that occurs in preeclampsia could liberate vWF from syncytiotrophoblast to the placental intervillous space, and this may have pathogenic implications.

Objective Inflammation plays a role in neurological alterations in patients with hepatic encephalopathy (HE). Animal models of HE show neuroinflammation. Treatment with ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces neuroinflammation and restores cognitive and motor function in rats with HE due to portacaval shunts (PCS). This suggests that reducing neuroinflammation would improve neurological status in patients with minimal or clinical HE. NSAID induce kidney damage in patients with cirrhosis and PCS rats and are not suitable for clinical use. It is therefore necessary to look for procedures to eliminate neuroinflammation without inducing secondary effects in the kidney. Inhibition of p38 MAPK is being tested as a therapeutic target in inflammatory diseases and reduces microglial activation. This study aimed to assess whether inhibiting p38 with SB239063 reduces neuroinflammation and improves cognitive and motor function in PCS rats without affecting the kidney. Results p38 activity is increased in the brains of PCS rats and treatment with SB239063 reduces microglial activation, as well as inflammatory markers in brain (prostaglandin E2, cyclooxygenase activity, iNOS, IL-1β, TNFα) and blood (prostaglandin E2 and TNFα). PCS rats showed increased ammonia and glutamine in the brain, which was not affected by SB239063. PCS rats showed reduced ability to learn a Y-maze conditional discrimination task, reduced motor activity and impaired motor coordination, as assessed in the rotarod. Treatment with SB239063 completely restored learning ability, motor activity and coordination in PCS rats. SB239063 did not affect creatinine or sodium levels in serum, indicating that it does not induce kidney damage. Conclusion These findings suggest that reducing neuroinflammation by using inhibitors of p38 would improve the neurological status in HE without inducing secondary effects in the kidney.

Rectus femoris injuries are extremely common in athletes, particularly in soccer players, rugby player, and sprinters. Magnetic resonance imaging (MRI) plays a key role in diagnosis, prognosis, and rehabilitation of these injuries. The current article discusses current concepts in the diagnosis and treatment of rectus femoris injuries in elite athletes, including a discussion of the less well known myofascial injuries and key prognostic factors as seen at MR imaging.

PURPOSE Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas (LASTS), although not standard, represents a promising option for resectable tumours. Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), HER2, excision repair cross-complementing group 1 (ERCC1) protein expression, histological response and clinical outcomes of LASTS patients. PATIENTS AND METHODS A retrospective study based on clinical data and archival paraffin-embedded tumour tissue at diagnosis from 78 consecutive LASTS patients treated with neo-adjuvant chemotherapy in our institution enabled analysis of ERCC1, HER2 and Topo2A protein expression by immuno-histochemistry. RESULTS Disease free survival (DFS) and overall survival (OS) were 48% and 64%, respectively. The annual risk of relapse increased with a higher percentage of residual identifiable cells (RIC). A higher Topo2A protein was associated with an improved rate of good HR (r=0.416) and with a decreased risk of relapse. Median DFS decreased with low Topo2A (p⩽0.042). The ERCC1 status had no impact on histological response while ERCC1 positive tumours correlated with a favourable OS (p ≤ 0.058). Patients with LASTS co-expressing Topo2A and ERCC1 had a significant better outcome (p=0.018). Topo2A was the only independent variable linked to a good HR (p ≤ 0.017); histological grade 3 was the only independent adverse prognostic variable linked to both DFS (p ≤ 0.04) and OS (p ≤ 0.004). CONCLUSIONS While histological response predicts better DFS, Topo2A protein expression correlates with histological response and better DFS. The combination of an early predictive factor for chemosensitivity (Topo2A) and for survival (ERCC1) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).

Hypertension is considered to be the most important risk factor in the development of cardiovascular disease. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), has a key role in the pathogenesis of hypertension. The modulation of the vasomotor system involves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1 and urotensin-II, among others. The bioavailability of nitric oxide (NO), which is a major vasodilator, is highly dependent on the redox status. Under physiological conditions, low concentrations of intracellular ROS have an important role in the normal redox signaling maintaining vascular function and integrity. However, under pathophysiological conditions, increased levels of ROS contribute to vascular dysfunction and remodeling through oxidative damage. In human hypertension, an increase in the production of superoxide anions and hydrogen peroxide, a decrease in NO synthesis and a reduction in antioxidant bioavailability have been observed. In turn, antioxidants are reducing agents that can neutralize these oxidative and otherwise damaging biomolecules. The use of antioxidant vitamins, such as vitamins C and E, has gained considerable interest as protecting agents against vascular endothelial damage. Available data support the role of these vitamins as effective antioxidants that can counteract ROS effects. This review discusses the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of vascular damage in hypertension, and the possible therapeutic strategies that could prevent or treat this disorder.