Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients.

Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure, an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.

Comparison of oxidative stress markers in HIV-infected patients on efavirenz or atazanavir/ritonavir-based therapy.

INTRODUCTION Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.

Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship. 2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capacities. 3. Populations of D. melanogaster were: (i) not subject to selection (control), (ii) selected for improved learning ability, (iii) selected for survival and fast development on poor food, or (iv) subject to both selection regimes. 4. There was no detectable response to selection for learning ability. 5. Selection on poor food led to higher survival, faster development and smaller adult size as a direct response, and to reduced learning ability as a correlated response. This study supports the hypothesis that adaptation to poor nutrition is likely to trade off with the evolution of improved learning ability.

The Impact of Personality and Culture on the Job Demands-Control Model of Job Stress

Among the various work stress models, one of the most popular has been the job demands-control (JDC) model developed by Karasek (1979), which postulates that work-related strain is highest under work conditions characterized by high demands and low autonomy. The absence of social support at work further increases negative outcomes. This model, however, does not apply equally to all individuals and to all cultures. This review demonstrates how various individual characteristics, especially some personality dimensions, influence the JDC model and could thus be considered buffering or moderator factors. Moreover, we review how the cultural context impacts this model as suggested by results obtained in European, American, and Asian contexts. Yet there are almost no data from Africa or South America. More crosscultural studies including populations from these continents would be valuable for a better understanding of the impact of the cultural context on the JDC model.

Tibial component positioning in total knee arthroplasty: bone coverage and extensor apparatus alignment.

Correct positioning of the tibial component in total knee arthroplasty (TKA) must take into account both an optimal bone coverage (defined by a maximal cortical bearing with posteromedial and anterolateral support) and satisfactory patellofemoral tracking. Consequently, a compromise position must be found by the surgeon during the operation to simultaneously meet these two requirements. Moreover, tibial tray positioning depends upon the tibial torsion, which has been shown to act mainly in the proximal quarter of the tibia. Therefore, the correct application of the tibial tray is also theoretically related to the level of bone resection. In this study, we first quantified the torsional profile given by an optimal bone coverage for a symmetrical tibial tray design and for an asymmetrical one. Then, for the two types of tibial trays, we measured the angle difference between optimal bone coverage and an alignment on the middle of the tibial tubercule. Results showed that the values of the torsional profile given by the symmetrical tray were more scattered than those from the asymmetrical one. However, determination of the mean differential angle between the position providing optimal bone coverage and the one providing the best patellofemoral tracking indicated that the symmetrical prosthetic tray offered the best compromise between these two requirements. Although the tibiofemoral joint is known to be asymmetric in both shape and dimension, the asymmetrical tray chosen in this study was found to fulfill this compromise with more difficulty.

Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets.

AIMS/HYPOTHESIS: Pro-atherogenic and pro-oxidant, oxidised LDL trigger adverse effects on pancreatic beta cells, possibly contributing to diabetes progression. Because oxidised LDL diminish the expression of genes regulated by the inducible cAMP early repressor (ICER), we investigated the involvement of this transcription factor and of oxidative stress in beta cell failure elicited by oxidised LDL. METHODS: Isolated human and rat islets, and insulin-secreting cells were cultured with human native or oxidised LDL or with hydrogen peroxide. The expression of genes was determined by quantitative real-time PCR and western blotting. Insulin secretion was monitored by EIA kit. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. RESULTS: Exposure of beta cell lines and islets to oxidised LDL, but not to native LDL raised the abundance of ICER. Induction of this repressor by the modified LDL compromised the expression of important beta cell genes, including insulin and anti-apoptotic islet brain 1, as well as of genes coding for key components of the secretory machinery. This led to hampering of insulin production and secretion, and of cell survival. Silencing of this transcription factor by RNA interference restored the expression of its target genes and alleviated beta cell dysfunction and death triggered by oxidised LDL. Induction of ICER was stimulated by oxidative stress, whereas antioxidant treatment with N-acetylcysteine or HDL prevented the rise of ICER elicited by oxidised LDL and restored beta cell functions. CONCLUSIONS/INTERPRETATION: Induction of ICER links oxidative stress to beta cell failure caused by oxidised LDL and can be effectively abrogated by antioxidant treatment.

Desenvolupament d’un nou component de gestió de clients i facturació d’una immobiliària per Joomla

Disseny i implementació d’ una aplicació per incorporar noves funcionalitats a la gestió de propietats immobles. En els últims anys, el lloguer d’apartaments i cases ha augmentat el seu volum de reserves a través d’Internet, i és per això, que moltes empreses del sector han dedicat molts esforços en potenciar aquest canal i fer tots els tràmits a través de la xarxa. L’hivern del 2009 l’empresa a qui va dirigida aquest projecte, va decidir fer aquest salt i irrompre a Internet. En aquell moment es van plantejar diferents opcions per a la gestió d’immobles: fer una aplicació totalment nova i a mida, comprar una aplicació ja feta a empreses especialitzades o adaptar una aplicació gratuïta a les necessitats de l’empresa. Analitzats amb detall els tres casos, es va decidir implementar la tercera opció ja que satisfeia les necessitats de l’empresa i amb modificacions o adaptacions aconseguiria el resultat esperat. L’aplicació gratuïta és el “com-property” i la seva posada en marxa va ser en dos mesos

The influence of attachment on perceived stress and cortisol response to acute stress in women sexually abused in childhood or adolescence.

The long-term implications of sexual abuse in childhood or adolescence (CSA) have been relatively well documented regarding attachment (disorganized attachment in childhood, unresolved trauma in adulthood), stress reactions (altered patterns of stress reactivity under experimental conditions), and psychopathology. Attachment has been shown to mediate the implications of CSA, namely on psychopathology. The implication of attachment on stress responses of abused persons has not been documented. Twenty-seven 20-46 years old women who had experienced episodes of CSA, and 17 controls have been interviewed using the Adult Attachment Interview. Sixty-three percent of abused women presented an unresolved trauma (12% for the controls). Thirty-six women (14 controls and 22 abused) came again to the laboratory for a session involving an experimental stress challenge (TSST). Subjects provided repeated appreciations of perceived stress on visual analogue scales and saliva samples were collected to assay cortisol levels. Whereas abused women with unresolved trauma showed the highest levels of perceived stress, they simultaneously presented the most suppressed cortisol reactions (there were significant post hoc differences between "unresolved abused" and controls on the increase of perceived stress and on cortisol recovery after the acute stress). It is suggested that important stressful experiences (such as CSA), especially when they have not been psychologically assimilated, may cause a disconnection, during subsequent mildly stressful circumstances, between the perception of stress and natural defensive body reactions.

Early-Life Insults Impair Parvalbumin Interneurons via Oxidative Stress: Reversal by N-Acetylcysteine.

BACKGROUND: A hallmark of the pathophysiology of schizophrenia is a dysfunction of parvalbumin-expressing fast-spiking interneurons, which are essential for the coordination of neuronal synchrony during sensory and cognitive processing. Oxidative stress as observed in schizophrenia affects parvalbumin interneurons. However, it is unknown whether the deleterious effect of oxidative stress is particularly prevalent during specific developmental time windows. METHODS: We used mice with impaired synthesis of glutathione (Gclm knockout [KO] mice) to investigate the effect of redox dysregulation and additional insults applied at various periods of postnatal development on maturation and long-term integrity of parvalbumin interneurons in the anterior cingulate cortex. RESULTS: A redox dysregulation, as in Gclm KO mice, renders parvalbumin interneurons but not calbindin or calretinin interneurons vulnerable and prone to exhibit oxidative stress. A glutathione deficit delays maturation of parvalbumin interneurons, including their perineuronal net. Moreover, an additional oxidative challenge in preweaning or pubertal but not in young adult Gclm KO mice reduces the number of parvalbumin-immunoreactive interneurons. This effect persists into adulthood and can be prevented with the antioxidant N-acetylcysteine. CONCLUSIONS: In Gclm KO mice, early-life insults inducing oxidative stress are detrimental to immature parvalbumin interneurons and have long-term consequences. In analogy, individuals carrying genetic risks to redox dysregulation would be potentially vulnerable to early-life environmental insults, during the maturation of parvalbumin interneurons. Our data support the need to develop novel therapeutic approaches based on antioxidant and redox regulator compounds such as N-acetylcysteine, which could be used preventively in young at-risk subjects.

The role of C-Jun N-terminal kinase in a mouse model of intracerebral hemorrhage

Background: Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by a haematoma within the brain parenchyma resulting from blood vessel rupture and with a poor outcome. In ICH, the blood entry into the brain triggers toxicity resulting in a substantial loss of neurons and an inflammatory response. At the same time, blood-brain barrier (BBB) disruption increases water content (edema) leading to growing intracranial pressure, which in turn worsens neurological outcome. Although the clinical presentation is similar in ischemic and hemorrhagic stroke, the treatment is different and the stroke type needs to be determined beforehand by imaging which delays the therapy. C-Jun N-terminal kinases (JNKs) are a family of kinases activated in response to stress stimuli and involved in several pathways such as apoptosis. Specific inhibition of JNK by a TAT-coupled peptide (XG-102) mediates strong neuroprotection in several models of ischemic stroke in rodents. Recently, we have observed that the JNK pathway is also activated in a mouse model of ICH, raising the question of the efficacy of XG-102 in this model. Method: ICH was induced in the mouse by intrastriatal injection of bacterial collagenase (0,1 U). Three hours after surgery, animals received an intravenous injection of 100 mg/kg of XG-102. The neurological outcome was assessed everyday until sacrifice using a score (from 0 to 9) based on 3 behavioral tests performed daily until sacrifice. Then, mice were sacrificed at 6 h, 24 h, 48 h, and 5d after ICH and histological studies performed. Results: The first 24 h after surgery are critical in our ICH mice model, and we have observed that XG-102 significantly improves neurological outcome at this time point (mean score: 1,8 + 1.4 for treated group versus 3,4+ 1.8 for control group, P<0.01). Analysis of the lesion volume revealed a significant decrease of the lesion area in the treated group at 48h (29+ 11mm3 in the treated group versus 39+ 5mm3 in the control group, P=0.04). XG-102 mainly inhibits the edema component of the lesion. Indeed, a significant inhibition Journal of Cerebral Blood Flow & Metabolism (2009) 29, S490-S493 & 2009 ISCBFM All rights reserved 0271-678X/09 $32.00 www.jcbfm.com of the brain swelling was observed in treated animals at 48h (14%+ 13% versus 26+ 9% in the control group, P=0.04) and 5d (_0.3%+ 4.5%versus 5.1+ 3.6%in the control group, P=0.01). Conclusions: Inhibition of the JNK pathway by XG- 102 appears to lead to several beneficial effects. We can show here a significant inhibition of the cerebral edema in the ICH model providing a further beneficial effect of the XG-102 treatment, in addition to the neuroprotection previously described in the ischemic model. This result is of interest because currently, clinical treatment for brain edema is limited. Importantly, the beneficial effects observed with XG-102 in models of both stroke types open the possibility to rapidly treat stroke patients before identifying the stroke subtype by imaging. This will save time which is precious for stroke outcome.

Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

The aim of this study was to evaluate adverse effects of multiwalled carbon nanotubes (MWCNT), produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in two other media: ethanol (EtOH) and phosphate-buffered saline (PBS). Effects of MWCNT were also compared to those of two asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells but also in mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15-35 μm2) that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress was observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability, and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. [Authors]

Anastomotic longitudinal stress due to modification of arterial longitudinal properties after anastomosis.

BACKGROUND: In our hands, in vivo segmental vessel length changes up to 5% because of blood pressure: increasing in arterial pressure is associated to decrease in segmental vessel length. METHODS AND MATERIAL: Using two piezoelectric crystals sutured on vessel wall and a high fidelity pressure probe, we recorded artery length variations as function of blood pressure, before and after an end-to-end anastomosis on four pigs carotid arteries. RESULTS: Mean arterial pressure before anastomosis = 73 mmHg (+/- 12); mean arterial pressure after anastomosis = 91 mmHg (+/- 14); mean crystals displacement before anastomosis during systole = -0.21 mm; mean crystals displacement after anastomosis during systole = +0.24 mm; mean distance between crystals before anastomosis = 12.3 mm (+/- 0.8) and after anastomosis = 11.2 mm (+/- 0.5). CONCLUSIONS: In the acute phase following an end-to-end anastomosis, an increase in blood pressure causes increasing in vessel length, with an exponential correlation. The anastomosis is constantly subjected to a longitudinal traction whose magnitude depends on blood pressure.