C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment

Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120 mmHg for 45 min, which was followed by 15 min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15 min. In the RBM exposed to 3 mM phosphate and/or 100 mu M Ca2+, C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment. (C) 2012 Elsevier Inc. All rights reserved.

Preoperative 6-min walking distance does not predict pulmonary complications in upper abdominal surgery

Background and objective: Field exercise tests have been increasingly used for pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test commonly employed in clinical practice; however, there is limited evidence supporting its use as a risk assessment method in abdominal surgery. The aim was to assess if the 6MWD can predict the development of post-operative pulmonary complications (PPCs) in patients having upper abdominal surgery (UAS). Methods: This prospective cohort study included 137 consecutive subjects undergoing elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their performance were compared with predicted values of 6MWD (p6MWD) using a previously validated formula. PPCs (including pneumonia, tracheobronchitis, atelectasis with clinical repercussions, bronchospasm and acute respiratory failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD and p6MWD were compared between subjects who developed PPC (PPC group) and those who did not (no PPC group) using Student's t-test. Results: Ten subjects experienced PPC (7.2%) and no significant difference was observed between the 6MWD obtained in the PPC group and no PPC group (466.0 +/- 97.0 m vs 485.3 +/- 107.1 m; P = 0.57, respectively). There was also no significant difference observed between groups for the p6MWD (100.7 +/- 29.1% vs 90.6 -/+ 20.9%; P > 0.05). Conclusions: The results of the present study suggest that the 6-min walking test is not a useful tool to identify subjects with increased risk of developing PPC following UAS.

Shape isomerism and shape coexistence effects on the Coulomb energy differences in the N = Z nucleus As-66 and neighboring T=1 multiplets

Excited states of the N = Z = 33 nucleus As-66 have been populated in a fusion-evaporation reaction and studied using gamma-ray spectroscopic techniques. Special emphasis was put into the search for candidates for the T = 1 states. A new 3(+) isomer has been observed with a lifetime of 1.1(3) ns. This is believed to be the predicted oblate shape isomer. The excited levels are discussed in terms of the shell model and of the complex excited Vampir approaches. Coulomb energy differences are determined from the comparison of the T = 1 states with their analog partners. The unusual behavior of the Coulomb energy differences in the A = 70 mass region is explained through different shape components (oblate and prolate) within the members of the same isospin multiplets. This breaking of the isospin symmetry is attributed to the correlations induced by the Coulomb interaction.

The impact of the medical speciality in primary health-care problem solving in Belo Horizonte, Brazil: homeopaths versus family doctors: a preliminary quantitative study

Introduction: This research project examined influence of the doctors' speciality on primary health care (PHC) problem solving in Belo Horizonte (BH) Brazil, comparing homeopathic with family health doctors (FH), from the management's and the patients' viewpoint. In BH, both FH and homeopathic doctors work in PHC. The index of resolvability (IR) is used to compare resolution of problems by doctors. Methods: The present research compared IR, using official data from the Secretariat of Health and test requests made by the doctors and 482 structured interviews with patients. A total of 217,963 consultations by 14 homeopaths and 67 FH doctors between 1 July 2006 and 30 June 2007 were analysed. Results: The results show significant differences greater problem resolution by homeopaths compared to FH doctors. Conclusion: In BH, the medical speciality, homeopathy or FH, has an impact on problem solving, both from the managers' and the patients' point of view. Homeopaths request fewer tests and have better IR compared with FH doctors. Specialisation in homeopathy is an independent positive factor in problem solving at PHC level in BH, Brazil. Homeopathy (2012) 101, 44-50.

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation

Purpose Intestinal mucositis and the closely associated diarrhea are common costly side effects of irinotecan. Cytokine modulators, such as thalidomide and pentoxifylline, are found capable of attenuating intestinal mucositis progression. Nitric oxide (NO) seems to be a key mediator of the antineoplastic drug toxicity. The aim of this study was to investigate the role of NO on the pathogenesis of intestinal mucositis, as well as the participation of cytokines upon inducible nitric oxide synthase (iNOS) expression in irinotecan-induced intestinal mucositis. Methods iNOS-knockout (iNOS(-/-)) and C57BL/6 (WT, wild type) animals (n = 5-6) were given either saline or irinotecan (60 mg/kg i.p for 4 days), with or without pretreatment with aminoguanidine (50 mg/kg s.c.), thalidomide (60 mg/kg s.c), infliximab (5 mg/kg i.v.), or pentoxifylline (1.7 mg/kg s.c). On day 5, diarrhea was assessed, and following euthanasia, proximal intestinal samples were obtained for myeloperoxidase (MPO) and iNOS activity, morphometric analysis, western blot and immunohistochemistry to iNOS, cytokine dosage, and for in vitro evaluation of gut contractility. Results Irinotecan induced severe diarrhea and intestinal smooth muscle over-contractility, accompanied with histopathological changes. Additionally, increased MPO and iNOS activity and iNOS immunoexpression were found in WT animals treated with irinotecan. The rise in MPO, smooth muscle over-contractility, and diarrhea were abrogated in aminoguanidine-treated and iNOS(-/-) mice. Moreover, through western blot, we verified that infliximab and pentoxifylline significantly inhibited irinotecan-induced iNOS expression. In addition, cytokine concentration was found only partially decreased in irinotecan-treated iNOS(-/-) mice when compared with wild-type animals that were given irinotecan. Conclusions This study suggests a role of nitric oxide in the pathogenesis of irinotecan-induced intestinal mucositis and also provides evidence for the participation of cytokines on iNOS induction.

Effects of active and passive lacebacks on antero-posterior position of maxillary first molars and central incisors

The purpose of this study was to compare the effects of active and passive lacebacks on antero-posterior position of maxillary first molars and central incisors during leveling phase. Twenty-three subjects with Class I and Class II malocclusion were treated with first premolars extraction using preadjusted appliances (MBT 0.022-inch brackets). The leveling phase was performed with stainless steel archwires only. The sample was divided into 2 groups: 14 subjects received active lacebacks (Group 1) and 9 subjects received passive lacebacks (Group 2). Lacebacks were made from 0.008-inch ligature wire. Lateral cephalometric radiographs were taken pre- and post-leveling phase. Student's t-test was applied to determine the differences between pre- and post-leveling mean values and to determine the mean differences between groups. In Group I, the first molars showed a significant mesial movement, whereas no change was observed in Group 2. In both groups, maxillary central incisor crowns moved to lingual side. In conclusion, active laceback produced anchorage loss of maxillary first molars whereas passive laceback did not affect the position of these teeth. Active and passive lacebacks were effective in preventing central incisor proclination.

Fluxes of CO2 above a sugarcane plantation in Brazil

Fluxes of CO2 were measured above a sugarcane plantation using the eddy-covariance method covering two growth cycles, representing the second and third re-growth (ratoons) harvested with stubble burning. The total net ecosystem exchange (NEE) in the first cycle (second ratoon, 393 days long) was −1964 ± 44 g C m−2; the gross ecosystem productivity (GEP) was 3612 ± 46 g C m−2 and the ecosystem respiration (RE) was 1648 ± 14 g C m−2. The NEE and GEP totals in the second cycle (third ratoon, 374 days long) decreased 51% and 25%, respectively and RE increased 7%. Accounting for the carbon emitted during biomass burning and the removal of stalks at harvest, net ecosystem carbon balance (NECB) totals were 102 ± 130 g C m−2 and 403 ± 84 g C m−2 in each cycle respectively. Thus the sugarcane agrosystem was approximately carbon neutral in the second ratoon. Yield in stalks fresh weight (SFW) attained the regional average (8.3 kg SFW m−2). Although it was a carbon source to the atmosphere, observed productivity (6.2 kg SFW m−2) of the third ratoon was 19% lower than the regional average due to the lower water availability observed during the initial 120 days of re-growth. However, the overall water use efficiency (WUE) achieved in the first cycle (4.3 g C kg−1 H2O) decreased only 5% in the second cycle. © 2013 Elsevier B.V. All rights reserved

Septin C-Terminal Domain Interactions: Implications for Filament Stability and Assembly

Septins form a conserved family of filament forming GTP binding proteins found in a wide range of eukaryotic cells. They share a common structural architecture consisting of an N-terminal domain, a central GTP binding domain and a C-terminal domain, which is often predicted to adopt a coiled-coil conformation, at least in part. The crystal structure of the human SEPT2/SEPT6/SEPT7 heterocomplex has revealed the importance of the GTP binding domain in filament formation, but surprisingly no electron density was observed for the C-terminal domains and their function remains obscure. The dearth of structural information concerning the C-terminal region has motivated the present study in which the putative C-terminal domains of human SEPT2, SEPT6 and SEPT7 were expressed in E. coli and purified to homogeneity. The thermal stability and secondary structure content of the domains were studied by circular dichroism spectroscopy, and homo- and hetero-interactions were investigated by size exclusion chromatography, chemical cross-linking, analytical ultracentrifugation and surface plasmon resonance. Our results show that SEPT6-C and SEPT7-C are able to form both homo- and heterodimers with a high alpha-helical content in solution. The heterodimer is elongated and considerably more stable than the homodimers, with a K (D) of 15.8 nM. On the other hand, the homodimer SEPT2-C has a much lower affinity, with a K (D) of 4 mu M, and a moderate alpha-helical content. Our findings present the first direct experimental evidence toward better understanding the biophysical properties and coiled-coil pairings of such domains and their potential role in filament assembly and stability.

Analysis of confinement potential fluctuation and band-gap renormalization effects on excitonic transition in GaAs/AlGaAs multiquantum wells grown on (100) and (311)A GaAs surfaces

The competition between confinement potential fluctuations and band-gap renormalization (BGR) in GaAs/AlxGa1-xAs quantum wells grown on [1 0 0] and [3 1 1]A GaAs substrates is evaluated. The results clearly demonstrate the coexistence of the band-tail states filling related to potential fluctuations and the band-gap renormalization caused by an increase in the density of photogenerated carriers during the photoluminescence (PL) experiments. Both phenomena have strong influence on temperature dependence of the PL-peak energy (E-PL(T)). As the photon density increases, the E-PL can shift to either higher or lower energies, depending on the sample temperature. The temperature at which the displacement changes from a blueshift to a redshift is governed by the magnitude of the potential fluctuations and by the variation of BGR with excitation density. A simple band-tail model with a Gaussian-like distribution of the density of state was used to describe the competition between the band-tail filling and the BGR effects on E-PL(T). (C) 2012 Elsevier B.V. All rights reserved.

Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. (c) 2012 Elsevier Ltd. All rights reserved.

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

Star formation in H I tails: HCG 92, HCG 100 and six interacting systems

We present new Gemini spectra of 14 new objects found within the H?i tails of Hickson Compact Groups (HCGs) 92 and 100. Nine of them are Galaxy Evolution Explorer (GALEX) far-ultraviolet (FUV) and near-ultraviolet (NUV) sources. The spectra confirm that these objects are members of the compact groups and have metallicities close to solar, with an average value of 12+log(O/H) similar to 8.5. They have average FUV luminosities 7 x 10(40)?erg?s-1 and very young ages (<100?Myr), and two of them resemble tidal dwarf galaxy (TDG) candidates. We suggest that they were created within gas clouds that were ejected during galaxygalaxy interactions into the intergalactic medium, which would explain the high metallicities of the objects, inherited from the parent galaxies from which the gas originated. We conduct a search for similar objects in six interacting systems with extended H?i tails: NGC 2623, NGC 3079, NGC 3359, NGC 3627, NGC 3718 and NGC 4656. We found 35 ultraviolet (UV) sources with ages < 100?Myr; however, most of them are on average less luminous/massive than the UV sources found around HCG 92 and HCG 100. We speculate that this might be an environmental effect and that compact groups of galaxies are more favourable to TDG formation than other interacting systems.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) phosphorylation by protein kinase Cδ (PKCδ) inhibits mitochondria elimination by lysosomal-like structures following ischemia and reoxygenation-induced injury

Background: How damaged mitochondria are removed by mitophagy is not fully described. Results: Ischemia and reoxygenation (I/R)-induced injury triggers mitochondria association of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and mitophagy, and protein kinase Cδ (PKCδ) activation inhibits it. Conclusion: PKCδ-mediated phosphorylation of GAPDH inhibits mitophagy. Significance: GAPDH/PKCδ is a signaling switch, which is activated during ischemic injury to regulate the balance between cell survival by mitophagy and cell death by apoptosis.