A model of traumatic brain injury in rats is influenced by neuroprotection of diurnal variation which improves motor behavior and histopathology in white matter myelin.

Traumatic brain injury (TBI) represents a significant public health concern and has been associated with high rates of morbidity and mortality. TBI generates two types of brain damage: primary and secondary. Secondary damage originates a series of pathophysiological processes, which include metabolic crisis, excitotoxicity, and neuroinflammation, which have deleterious consequences for neuronal function. However, neuroprotective mechanisms are also activated. The balance among these tissue responses, and its variations throughout the day determines the fate of the damage tissue. We have demonstrated less behavioral and morphological damage when a rat model of TBI was induced during the light hours of the day. Moreover, here we show that rats subjected to TBI in the dark lost less body weight than those subjected to TBI in the light, despite no change in food intake. Besides, the rats subjected to TBI in the dark had better performance in the beam walking test and presented less histological damage in the corpus callosum and the cingulum bundle, as shown by the Klüver-Barrera staining. Our results suggest that the time of day when the injury occurs is important. Thus, this data should be used to evaluate the pathophysiological processes of TBI events and develop better therapies.

EZH2 mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment.

EZH2 is mutated in nearly 25% of follicular lymphoma (FL) cases. Little is known about how EZH2 affects patients' response to therapy. In this context, the aim of this study was to retrospectively analyze the frequency of mutations in EZH2 at diagnosis in tissue and ctDNA in patients with FL and to assess the patients' outcomes after receiving immunochemotherapy, depending on the EZH2 mutation status. Among the 154 patients included in the study, 27% had mutated EZH2 (46% with high-grade and 26% with low-grade FL). Of the mutated tissue samples, the mutation in ctDNA was identified in 44% of cases. EZH2 mutation in ctDNA was not identified in any patient unmutated in the tissue.Unmutated patients who received R-CHOP had significantly more relapses than patients who received R-Bendamustine (16/49 vs. 2/23, p = 0.040). Furthermore, our results show that patients with mutated EZH2 treated with R-CHOP vs. those treated with R-Bendamustine present a lower incidence of relapse (10% vs. 42% p = 0.09 at 4 years), a higher PFS (92% vs. 40% p = 0.039 at 4 years), and higher OS (100% vs. 78% p = 0.039 at 4 years). Based on these data, RCHOP could be a more suitable regimen for mutated patients, and R-bendamustine for unmutated patients. These findings could mean the first-time identification of a useful biomarker to guide upfront therapy in FL.

Anthropogenic and natural variability in the composition of sedimentary organic matter of the urbanised coastal zone of Montevideo (Río de la Plata).

This study is aimed to identify the different sources of sedimentary organic matter (SOM) within Montevideo coastal zone (MCZ). To this end δ13C, δ15N and C/N ratio were analysed in surface sediments and a sediment core. Sediment core analysis showed that until ~1950CE SOM was mainly marine, observing a shift towards lower δ13C in recent sediments, evidencing an estuarine composition. This trend was associated to the climatic variability, which exerted a major influence on the SOM composition, leading to an increased input of terrigenous material and associated anthropogenic contaminants. Surface sediments collected during different El Niño South Oscillation (ENSO) phases did not show inter-annual variability in SOM composition, which was mainly marine in both eastern and western region of MCZ and estuarine in Montevideo Bay. This spatial pattern provides new insights on the dynamics and factors affecting organic matter sources available for primary consumers along the study region.

Indoleamine 2,3 dioxygenase as a prognostic and follow-up marker in melanoma. A comparative study with LDH and S100B.

BACKGROUND: To date, lactate dehydrogenase (LDH) and S100B remain the most useful biomarkers for follow-up of melanoma patients. In recent years, indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme, has been proposed as a new potential tumour biomarker for melanoma. However, further studies are needed to confirm the usefulness of IDO expression as an independent prognostic factor. OBJECTIVE: To explore the potential association between serum IDO levels and melanoma stage at diagnosis and recurrence, and to compare the results to those obtained with LDH and S100B. In addition, we also investigated a possible cut off for IDO level as a prognostic factor for overall survival. METHODS: IDO, LDH and S100B levels were measured in serum samples of 186 patients in all melanoma stages at diagnosis and twice a year thereafter. A cut-off point for IDO levels was calculated using receiver operating characteristic curves to explore the association between these levels and the likelihood of lymphatic spread. Survival curves were estimated for patient groups stratified by IDO level (higher or lower than the cut off), using the Kaplan-Meier method. RESULTS: At diagnosis, serum IDO levels were significantly higher in stages IB, II, III and IV, whereas S100B levels were significantly higher in stages III and IV, and LDH levels were only higher in stage IV. In relapsed patients, significant increases were found in levels of all three markers. Finally, overall survival was significantly longer in patients with IDO levels below a cut off of 1.65 µM at diagnosis than in those with higher levels (91.3 vs. 71.0% at 36 months). CONCLUSION: In melanoma patients, serum IDO levels are significantly associated with disease stage, relapses and overall survival. These results indicate IDO could be a useful serum prognostic marker for melanoma.

Historical economic and environmental policies influencing trace metal inputs in Montevideo Bay, Río de la Plata.

Montevideo Bay is located in the middle zone of the Rio de la Plata, and since the foundation of the city, several key economic and environmental policies affected the industry, and thus, metal inputs into this ecosystem. The aim of this study is to evaluate the sedimentary geochemical record of Montevideo Bay, in order to determine the historical inputs of anthropogenic metals to the system. In addition, environmental and economic policies of the country were taken into account to infer the relationship between them and the historic metal input. Concentrations of aluminum, chromium, copper, lead, scandium and zinc were analyzed and the EF and SPI indices were calculated. The analysis showed that since Montevideo foundation, metal concentrations increased in accordance with industry development, and the indices as well as the metal concentration represent a reliable footprint of the history of different economic and environmental policies influencing historical industrial activities.

Evolution of Socioeconomic Conditions and Its Relation to Spatial-Temporal Changes of Giardiasis and Helminthiasis in Amazonian Children.

This study analyzed the evolution of socioeconomic, sanitary, and personal factors as well as spatiotemporal changes in the prevalence of helminthiasis and giardiasis in urban Amazonian children between 2003 and 2011. Child age, lack of sanitation, and lack of access to bottled water were identified as significant associated factors for helminthiasis and giardiasis. There was an overall improvement in socioeconomic and sanitary conditions in the city resulting in decreased helminth prevalences from 12.42 to 9.63% between 2003 and 2010, but the prevalence increased to 15.03% in 2011 due to migratory movement and unstable sanitary conditions. As for Giardiasis, socioeconomic and environmental changes were not enough to reduce prevalence (16% in 2003 and 23% in 2011). Spatial analysis identified a significant cluster for helminthiasis in an area of poor housing conditions. Control programs in the Amazon need to target high-risk areas focusing changes in sanitation, water usage, and health education.

Sewage contamination in a tropical coastal area (São Sebastião Channel, SP, Brazil).

Urban effluent discharges in Brazilian coastal areas are a chronic problem and often lead to changes in the quality of the marine environment. São-Sebastião-Channel (SSC) is an important aquatic ecosystem to be monitored for urban sewage contamination due to the intense urban activities in that region, as well as the relative high biodiversity of marine organisms. In the area are present three submarine sewage outfalls, a commercial harbour and also the biggest oil terminal in Brazil. Total organic carbon (TOC), total nitrogen (TN), total sulphur (TS), steroids and linear alkylbenzenes (LABs) were measured in sediment samples collected in three strategic locations of the SSC in order to monitor urban sewage contamination. Total LAB and total sterols levels ranged from below DL-51.3 ng g(-1) and below DL-10.40 µg g(-1), respectively. Samples collected near sewage outfall in the central part of the SSC had higher concentrations of urban sewage-associated contaminants.

Assessing the ecological quality status of a temperate urban estuary by means of benthic biotic indices.

Benthic indices are commonly used tools for assessing the environmental quality, because they represent a simple source of scientific information. However, their performance could vary depending on the application area and perturbation types, thus they should be tested before used in other remote geographic regions. This study aims to test the use of some of the most widely common benthic biotic indices for assessing the environmental quality of Montevideo's coastal zone at a seasonal scale against many physicochemical variables. From all the evaluated indices, AMBI appears to be the most suitable one to assess the environmental quality. The study also allowed us to infer the most relevant physicochemical variables: protein, lipid and heavy metal sediment concentration. Additionally, site-specific threshold effect levels for heavy metals and biopolymers were established, which appear to be useful to determine tolerable levels of such stressors in future assessments or monitoring programs for the study area.

The effect of urban sewage on benthic macrofauna: a multiple spatial scale approach.

We investigated the spatial scales of variation of macrofauna in intertidal flats subjected to different levels of contamination from urban effluents in two areas sampled in the Paranaguá Estuarine Complex. The scales considered were: Conditions; Tidal flats and Plots. Although the numerically dominant taxa showed the greatest variability at a scale of Tidal flats, the variability at the Condition scale was also significant. Tubificinae sp. 1, Laeonereis culveri and Heteromastus sp. were the most abundant organisms in the Contaminated area, while Heleobia australis was most abundant in the Non-contaminated area. Our results, contrary to those frequently observed in the literature, showed that the variability was significant at the scale of hundreds of metres (Tidal flats). At this scale, the intrinsic characteristics of each tidal flat are more important in determining macrofaunal distribution, while the effects of the urban sewage contamination represent the primary forces acting at a greater spatial scale.

Cancer chemotherapy reduces plasma total polyphenols and total antioxidants capacity in colorectal cancer patients.

Our aim was to investigate the effect of chemotherapy on plasma total antioxidant capacity and polyphenols in patients with colon cancer. Plasma samples were collected from 70 CRC patients under chemotherapy treatment, and 15 non-treated patients. The control group included 71 healthy individuals. Plasma ABTS and FRAP were measured as biomarkers of antioxidant total capacity and the total phenols as an indicator to determine the polyphenols levels in plasma. Treatment with chemotherapy protocols resulted in a significant decrease of ABTS (-24 %, p < 0.048), FRAP (-15 %, p < 0.046) and polyphenols (-46 %, p < 0.05) compared with the values of those not treated. The total antioxidant capacity was significantly lower (-18 % for ABTS and -12 % for FRAP) in patients with metastasis as compared with patients without metastasis. The plasma total phenols, were also decreased (-16 %, p = 0.005) in metastasis patients. The patients with colorectal cancer have decreased total antioxidant capacity and the values are lower in patients treated with chemotherapy. Furthermore, CEA tumor marker levels are associated with a lower plasma total antioxidant capacity, and therefore with the progress and development of the disease.

The effects of 1-year treatment with a haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) dialysis on biomarkers of oxidative stress in patients with chronic renal failure.

In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on inflammation and oxidative stress biomarkers, but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown. This is a randomised clinical study over 12 months involving 40 patients on haemodialysis, comparing the effect of HFR (n=25) dialysis with haemodialysis with polysulfone (HD-PS, n=15) on oxidative stress. Total antioxidant capacity, enzymatic antioxidant [superoxide dismutase (SOD), catalase and glutathione peroxidase], non-enzymatic (GSH) and biomarkers of oxidative stress (TBARs, carbonyl groups and 8-OH-dG) were evaluated. The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR, with a significant decrease in the enzyme SOD. In the oxidative stress biomarkers, an increase was seen in the levels of 8-OH-dG in patients on HD-PS dialysis but not in those treated with HFR. Throughout the year the changes in antioxidant levels and biomarkers of oxidative damage in patients dialysed with HFR were generally more modest and fluctuated less than those dialysed with HD-PS. Our study indicates that, in general, long-term dialysis with HFR does not modified antioxidant parameters or increases the oxidative damage to biomolecules. The HFR showed to be a biocompatible technique for long-term dialysis.

On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.

Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 µM) were tested in cerebellum and forebrain homogenates exposed to 5 µM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 µM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 µM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 µM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 µM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.

Presence of Maillard products in Spanish muffins and evaluation of colour and antioxidant potential.

Spanish muffins are bakery products widely consumed in Spain. During their elaboration process MRPs are formed, being partially responsible for muffin characteristics including their antioxidant capacity. The main aim of the study was evaluating the amount, colour and antioxidant capacity of different fractions of MRPs (low and high molecular weight) isolated from commercial muffins. The fraction of high molecular weight (melanoidins) showed to have a higher antioxidant capacity, measured by ABTS and FRAP, than LMW ones. Significant and relatively close correlations between colour parameters and antioxidant capacity were observed for global MRPs, but only occasionally when isolated fractions of melanoidins and LMW were studied. As summary, it can be said that global MRPs present in muffins, apart from contributing to colour and flavour, can also contribute significantly to muffin conservation, due to their appreciable antioxidant capacity, which seems to be directly correlated with of their colour, although this fact is not extrapolated to isolated fractions of melanoidins and LMW MRPs.

The oxidation of metal-capped Co cluster films under ambient conditions.

We report on the unexpected deterioration under ambient conditions of films of Co clusters capped with relatively thick (>100 nm) Cu (or Ti) layers deposited by either thermal evaporation or by radiofrequency sputtering. The magnetic character of the clusters, prepared by gas-phase condensation, allows monitoring the oxidation of the samples through the decay of the saturation magnetization, which takes place on a timescale of days. By contrast, diluted (<10 at.%) cluster-assembled granular Co:Cu films, prepared by co-deposition of the Co clusters with a Cu vapour, are perfectly stable under ambient conditions. We tentatively explain the oxidation of the cluster films as stemming from their very high porosity.

Dietary practices and nutritional status of 0-24-month-old children from Brazilian Amazonia.

OBJECTIVE: To assess the nutritional status and dietary practices of 0-24-month-old children living in Brazilian Amazonia. DESIGN: Cross-sectional study. Information on children's dietary intakes was obtained from diet history data. Weight and length were measured for anthropometric evaluation. Fe status was assessed using fasting venous blood samples; Hb, serum ferritin and soluble transferrin receptor concentrations were measured. SETTING: The towns of Assis Brasil and Acrelândia in the state of Acre, north-west Brazil. SUBJECTS: A total of sixty-nine randomly selected 0-24-month-old children. RESULTS: Of these children, 40.3 % were anaemic, 63.1 % were Fe-deficient, 28.1 % had Fe-deficiency anaemia and 11.6 % were stunted. Breast-feeding was initiated by 97.1 % of mothers, followed by early feeding with complementary foods. The dietary pattern reflected a high intake of carbohydrate-rich foods and cow's milk, with irregular intakes of fruit, vegetables and meat. All infants and 92.3 % of toddlers were at risk of inadequate Fe intakes. Fe from animal foods contributed on average 0.5 % and 14.3 % to total dietary Fe intake among infants and toddlers, respectively. CONCLUSIONS: Poor nutritional status and inadequate feeding practices in this study population reinforce the importance of exclusive breast-feeding during the first 6 months of life. Greater emphasis is required to improve the bioavailability of dietary Fe during complementary feeding practices.

Effect of a hemodiafiltration session with on-line regeneration of the ultrafiltrate on oxidative stress. Comparative study with conventional hemodialysis with polysulfone.

BACKGROUND: The influence of a dialysis session using hemodiafiltration with on-line regeneration of the ultrafiltrate (HFR) is compared with that of a conventional hemodialysis session with polysulfone (HD-PS) and with a group of healthy individuals. METHODS: Total antioxidant capacity (TAC), antioxidants, i.e., superoxide dismutase (SOD) glutathione peroxidase (GPX), reduced glutathione (GSH) and catalase, and biomarkers of oxidative stress were evaluated in plasma, whole blood and lymphocytes. RESULTS: The study showed decreased plasma TAC, decreased activities of antioxidant enzymes and decreased GSH levels along with increased thiobarbituric-acid-reactive substances and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in lymphocytes. The antioxidants and biomarkers of lipid and protein damage after dialysis sessions with HFR were similar or better than following HD-PS. Thus, the blood GPX activity was comparable to that of healthy controls and significantly better than following HD-PS. An increase in 8-OHdG levels was observed in the HD-PS group after dialysis but not in the HFR group. CONCLUSIONS: These results show that HFR induces less oxidative stress than HD-PS.

[Preoperative workup to assess indication for laparoscopic treatment in gastroesophageal reflux disease].

INTRODUCTION AND OBJECTIVES: antireflux surgery performed by an experienced surgeon is a maintenance option for patients with well-documented gastroesophageal reflux disease (GERD). Well-documented GERD is difficult to find, as GERD is a multifactorial disease in which the gastroesophageal junction, with its special anatomical and functional components, is important. In order to examine patient preoperative workups, and their indication for surgical treatment in GERD, we retrospectively studied patients who underwent a laparoscopic antireflux procedure. METHODS: preoperative workups in patients from our health care area who underwent a laparoscopic antireflux procedure from December 1997 to February 2007 were retrospectively analyzed. Data related to epidemiological findings, symptoms, morphologic and functional evaluation, medical therapy, and indication for surgical treatment were recorded and statistically analyzed by means of a bivariate test. Differences were significant when the p value was equal to or less than 0.05. RESULTS: 100 patients (50 % female, 51.31 +/- 13.53 years of age) underwent a laparoscopic antireflux surgery after 56.47 +/- 61.33 months with symptoms. Ninety-five percent of patients had an anatomical abnormality. The pH monitoring test diagnosed three quarters of cases. The most frequent indication for GERD treatment was persistent or recurrent esophagitis despite adequate medical treatment (52 cases). CONCLUSIONS: based on our preoperative workup, as described, 100 percent of subjects were well documented and diagnosed with GERD (both non-erosive reflux disease and erosive reflux disease), and their indication for laparoscopic treatment was retrospectively assessed in 94% of cases.

Contribution of anthocyanin fraction to the antioxidant properties of wine.

The wine is a beverage with an important antioxidant efficiency which is attributed to their bioactives compounds, especially polyphenols. The anthocyanins are the main phenolic compounds of red wine and its consumption has been partially related with the "French Paradox". The aim of the present work was to evaluate the contribution of the anthocyanins to the antioxidant properties of red wines. So, total antioxidant capacity (TAC), hydroxyl and superoxide scavenger activity and lipid peroxidation of 80 Spanish red wines and their anthocyanins fractions have been assessed for ABTS, DPPH, DMPD, and FRAP methods, hydroxyl radical (HRSA), superoxide radical scavenger activity (SRSA) and ABAP-lipid peroxidation (ABAP-LP). The results showed that free anthocyanins fraction are main responsible of the total antioxidant capacity of red wines correlated with electron transference processes. In similar way, free anthocyanins are the maximum responsible of HRSA scavenger activity of red wines, contributing less extensively to their SRSA capacity or to their protective action on lipid peroxidation. Furthermore, simple anthocyanins exert a low action in TAC process involved with proton transference. Glycosilated and methoxylic anthocyanins as malvidin-3-glucoside, seem to be the type of anthocyanins with higher participation on the antioxidant effect of red wine.