Kinetics of TNF-alpha and IFN-gamma mRNA expression in islets and spleen of NOD mice

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of pancreatic ß cells. Non-obese diabetic (NOD) mice spontaneously develop diabetes similar to the human disease. Cytokines produced by islet-infiltrating mononuclear cells may be directly cytotoxic and can be involved in islet destruction coordinated by CD4+ and CD8+ cells. We utilized a semiquantitative RT-PCR assay to analyze in vitro the mRNA expression of TNF-alpha and IFN-gamma cytokine genes in isolated islets (N = 100) and spleen cells (5 x 10(5) cells) from female NOD mice during the development of diabetes and from female CBA-j mice as a related control strain that does not develop diabetes. Cytokine mRNAs were measured at 2, 4, 8, 14 and 28 weeks of age from the onset of insulitis to the development of overt diabetes. An increase in IFN-gamma expression in islets was observed for females aged 28 weeks (149 ± 29 arbitrary units (AU), P<0.05, Student t-test) with advanced destructive insulitis when compared with CBA-j mice, while TNF-alpha was expressed in both NOD and CBA-j female islets at the same level at all ages studied. In contrast, TNF-alpha in spleen was expressed at higher levels in NOD females at 14 weeks (99 ± 8 AU, P<0.05) and 28 weeks (144 ± 17 AU, P<0.05) of age when compared to CBA-j mice. The data suggest that IFN-gamma and TNF-alpha expression in pancreatic islets of female NOD mice is associated with ß cell destruction and overt diabetes.1347135

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Bioequivalence Of Two Tablets Formulations Of Escitalopram Oxalate In Healthy Volunteers Under Fasting Conditions [bioequivalência De Duas Formulações De Oxalato De Escitalopram Comprimidos Em Voluntários Sadios Administradas Em Jejum]

This study was conducted in order to access the bioequivalence of two tablets containing escitalopram oxalate 10 mg. Thirty-two healthy, male and female volunteers took part in the randomized, two-way, crossover study, with a minimum washout period of 10 days. One tablet of either formulation was administered after a 10h overnight fasting. After dosing, serial blood samples were collected during a period of 144 hours. Plasma samples were analyzed for escitalopram by a validated liquid chromatography coupled with tandem mass spectrometry detection (LC-MS-MS). Pharmacokinetic parameters area under the plasma concentration time curve from time zero to the last non-zero concentration time (AUC0-t) and maximum observed concentration (Cmax) were the main evaluation criteria for bioequivalence assessment between formulations. Area under the curve form time zero to infinity (AUC 0-inf), time to Cmax (Tmax) and half-life (t1/2) were also evaluated. The 90% confidence intervals (CI) obtained by analysis of variance (ANOVA) did not show any significant difference between the two formulations and fell within the pre-defined range (96,91-106,79 for AUC0-t and 89,40-102,39 for Cmax) Bioequivalence between the two products was therefore concluded both in terms of rate and extent of absorption. © Copyright Moreira Jr. Editora.6611375379Dhillon, S., Scott, J.L., Plosker, G.L., Escitalopram - A Review of its Use in the Management of Anxiety Disorders (2006) CNS Drugs, 20 (9), pp. 763-790Rao, N., The Clinical Pharmacokinetics of Escitalopram (2007) Clin Pharmacokinet, 46 (4), pp. 281-290Soogard, B., Mengel, H., Rao, N., Ursen, F., The Pharmacokinetics of Escitalopram After Oral and Intravenous Administration of Single and Multiple doses to Healthy Volunteers (2005) J. Clin. 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Cochrane Database of Systematic Reviews. In The Cochrane Library, Issue, 3. , Art. No. CD006532. DOI: 10.1002/14651858.CD006532. pub2Montgomery, S.A., Möller, H.J., Is the significant superiority of escitalopram compared with other antidepressants clinically relevant? (2009) Int Clin Psychopharmacol, 24 (3), pp. 111-118Wade, A.G., Schlaepfer, T.E., Andersen, H.F., Kilts, C.D., Clinical milestones predict symptom remission over 6-month and choice of treatment of patients with major depressive disorder (MDD) (2009) J Psychiatr Res, 43, pp. 568-575Kasper, S., Spadone, C., Verpillat, P., Angst, J., Onset of action of escitalopram compared with other antidepressants: Results of a pooled analysis (2006) Int Clin Psychopharmacol, 21, pp. 105-110Healthcare Series Integrated Index. Drugdex Drugs Evaluation, , www.portaldapesquisa.com.br, MICROMEDEX®, Disponível emWingen, M., Bothmer, J., Langer, S., Ramaeker, J.G., Actual Driving Performance and Psychomotor function in Healthy volunteers After Acute and Subchronic Treatment with Escitalopram, Mirtazapine and Placebo: A Croosover Trail (2005) J Clin Psychiatry, 66 (4), pp. 436-443CDER, Center for Drug Evaluation and Research, US-FDA. Guidance for Industry: Bioanalytical Method Validation. 2001. Disponível em: http://www. fda.gov/Drugs/GuidanceComplianceRegulatory Information/Guidances/ ucm064964.htm(2003) Guia para validação de métodos analíticos e bioanalíticos. Resolução - RE no899, de 29 de maio de, , http://www.anvisa.gov.br/e-legis, Disponível emCDER, Center for Drug Evaluation and Research, US-FDA. Guidance for industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations. 2003. Disponível em: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ ucm064964.htmANVISA. Guia para provas de biodisponibilidade relativa/ bioequivalência de medicamentos. Resolução - RE no1170, de 19 de abril de 2006. Disponível em: http://www.anvisa.gov.br/e-legis