Effects of polymer-coated multi-wall carbon nanotubes on mouse RAW 264.7 macrophages

Surface characteristics (area, chemical reactivity) play an important role in cell response to nanomaterials. The aim of this study was to evaluate the oxidative and inflammatory effects of multi−wall carbon nanotubes (MWCNT) uncoated (P0) or coated with carboxylic polyacid or polystyrene polybutadiene polymetacrylate of methyl polymers (P1 and P2 respectively) on murine macrophages (RAW 264.7 cell line). Carbon black nanoparticles (CB, diameter 95 nm) and crocidolite fibers (diameter: 80 nm, length: < 10 μm) were used as controls. Surface functional groups present on MWCNTs were analyzed by Knudsen flow reactor. The amount of acidic sites was P1> P0> P2, for basic sites was P0> P1>> P2 and for oxidizable sites was P0> P2> P1. In contact with cells, P2 formed smaller aggregates than P0 and P1, which were of similar size. Optical microscopy showed the formation of vacuoles after exposure only to P0, P1 and crocidolite. Incubation of cells with P0, P1 and crocidolite fibers induced a significant and similar decrease in metabolic activity, whereas P2 and CB had no effect. Cell number and membrane permeability were unmodified by incubation with the different particles. Incubation of macrophages with P0, P1 and crocidolite induced a dose− and time−dependent increase in mRNA expression of oxidative stress marker (HO−1, GPX1) and inflammatory mediators (TNF−a, MIP−2). No such responses were observed with P2 and CB. In conclusion, MWCNT coated with a carboxylic polyacid polymer exerted similar oxidative and inflammatory effects to uncoated MWCNT. By contrast, no such effects were observed with MWCNT coated with a polystyrene−based polymer. This kind of coating could be useful to decrease MWCNT toxicity.

Granulocyte-macrophage colony-stimulating factor elicits bone marrow-derived cells that promote efficient colonic mucosal healing.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy is effective in treating some Crohn's disease (CD) patients and protects mice from colitis induced by dextran sulfate sodium (DSS) administration. However, its mechanisms of action remain elusive. We hypothesized that GM-CSF affects intestinal mucosal repair. METHODS: DSS colitic mice were treated with daily pegylated GM-CSF or saline and clinical, histological, and inflammatory parameters were kinetically evaluated. Further, the role of bone marrow-derived cells in the impact of GM-CSF therapy on DSS colitis was addressed using cell transfers. RESULTS: GM-CSF therapy reduced clinical signs of colitis and the release of inflammatory mediators. GM-CSF therapy improved mucosal repair, with faster ulcer reepithelialization, accelerated hyperproliferative response of epithelial cells in ulcer-adjacent crypts, and lower colonoscopic ulceration scores in GM-CSF-administered mice relative to untreated mice. We observed that GM-CSF-induced promotion of mucosal repair is timely associated with a reduction in neutrophil numbers and increased accumulation of CD11b(+) monocytic cells in colon tissues. Importantly, transfer of splenic GM-CSF-induced CD11b(+) myeloid cells into DSS-exposed mice improved colitis, and lethally irradiated GM-CSF receptor-deficient mice reconstituted with wildtype bone marrow cells were protected from DSS-induced colitis upon GM-CSF therapy. Lastly, GM-CSF-induced CD11b(+) myeloid cells were shown to promote in vitro wound repair. CONCLUSIONS: Our study shows that GM-CSF-dependent stimulation of bone marrow-derived cells during DSS-induced colitis accelerates colonic tissue repair. These data provide a putative mechanism for the observed beneficial effects of GM-CSF therapy in Crohn's disease.

Performance of the 47-Kilodalton Membrane Protein versus DNA Polymerase I Genes for Detection of Treponema pallidum by PCR in Ulcers.

Treponema pallidum PCR (Tp-PCR) is a direct diagnostic method for primary and secondary syphilis, but there is no recommendation regarding the best choice of target gene. In this study, we sequentially tested 272 specimens from patients with sexually transmitted ulcers using Tp-PCR targeting the tpp47 and then polA genes. The two methods showed similar accuracies and an almost-perfect agreement.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125 mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8 mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Impact of stressful life event on the global functioning outcome after an assertive community treatment

Background: Assertive community treatment (ACT) was reported to be an effective treatment to improve global functioning of ultra-high risk (UHR) adolescents. However, the infl uence of stressful life event (SLE) was not extensively studied which represent our objective. Method: The SLE (encompassing adoption, migration, family member's deceased, sexual or physical abuse, etc.) of 20 UHR adolescents, treated with an ACT model, were rated. 10 adolescents having 0 to 1 SLE (mainly parents' divorce; low SLE group) were compared 10 adolescents with 2 to 5 SLE (high SLE group). The adolescents were assessed at baseline and after treatment with the Health of Nation Outcome Scale for Children and Adolescents (HoNOSCA). The HoNOSCA allowed rating different diffi culties such as behavior, symptoms, disorders and social. Results: First, results on the whole sample indicated signifi cant improvement after ACT (compared to baseline) on the total (P = .04), symptoms (P = .025) and social (P = .009) scores of the HoNOSCA. Second, the improvement on the HoNOSCA's score of the high SLE group were signifi cantly higher for the total (P = .016), symptoms (P = .019) and behavior (P = .033) scores compared to the low SLE group. Discussion/Conclusion: Globally, ACT seems to be an appropriate treatment to enhance global functioning and more specifi cally the social and symptoms diffi culties of UHR adolescents. Additionally, UHR adolescents with a high numbers of SLE were observed to have a better benefi t of the ACT on global, symptoms and behavioral diffi culties.

Tous égaux devant Dieu ? Réflexions sur les logiques d'éligibilité des miraculés

Le pentecôtisme a fait du miracle le coeur de sa théologie et l'élément central de ses activités d'évangélisation. Le catholicisme, par contre, a toujours voulu contrôler l'ensemble des déclarations de manifestations divines. Apparitions et guérisons miraculeuses ont donc systématiquement, et de plus en plus, été soumises à de lentes et rigoureuses procédures d'authentification. Les pentecôtistes voient Dieu comme un être extérieur qui surgit sur la terre pour chasser le mal qui l'envahit. Tous les convertis ont donc droit à la libération et personne ne doit accepter sagement la souffrance. Or, les pèlerins catholiques que nous avons étudiés ne partagent pas ces convictions pentecôtistes. Dieu agit de l'intérieur, non pas en les délivrant, mais en les soutenant dans leurs épreuves quotidiennes. Rare et peu recherchée, la guérison physique cède la place à la guérison spirituelle, accessible à tous. Il nous semble que ces deux types de représentations placent les fidèles dans des dispositions d'esprit très divergentes suscitant, dans un cas ou dans l'autre, des espoirs adaptés à la capacité du groupe à produire des miracles. Pentecostalism placed miracles at the centre of its theology as a key element of its evangelization activities. Catholicism, on the other hand, has always tried to control all declarations of divine demonstrations. Miraculous appearances and recoveries have been more and more systematically subjected to slow and rigorous procedures of verification. The Pentecostals see God as an external force which manifests itself on earth to drive out the evil which invades it. All believers have the right to be free from evil, and nobody should have to accept pain meekly. But the Catholic pilgrims we studied do not share these Pentecostal convictions. God acts from inside, not by delivering them but by supporting them in their daily tests. Physical recovery is rare and not very sought after so it takes second place to spiritual recovery which is accessible to everyone. It seems to us that these two types of representation place believers in very divergent frames of mind giving rise, in one group or the other, to hopes that correspond to the group's capacity to produce miracles.