Ibuprofen-loaded calcium phosphate granules : combination of innovative characterization methods to relate mechanical strength to drug location

This paper studies the impact of the location of a drug substance on the physicochemical and mechanical properties of two types of calcium phosphate granules loaded with seven different contents of ibuprofen, ranging from 1.75% to 46%. These implantable agglomerates were produced by either low or high shear granulation. Unloaded Mi-Pro pellets presented higher sphericity and mechanical properties, but were slightly less porous than Kenwood granules (57.7% vs 61.2%). Nevertheless, the whole expected quantity of ibuprofen could be integrated into both types of granules. A combination of surface analysis, using near-infrared (NIR) spectroscopy coupling chemical imaging, and pellet porosity, by mercury intrusion measurements, allowed ibuprofen to be located. It was shown that, from 0% to 22% drug content, ibuprofen deposited simultaneously on the granule surface, as evidenced by the increase in surface NIR signal, and inside the pores, as highlighted by the decrease in pore volume. From 22%, porosity was almost filled, and additional drug substance coated the granule surfaces, leading to a large increase in the surface NIR signal. This coating was more regular for Mi-Pro pellets owing to their higher sphericity and greater surface deposition of drug substance. Unit crush tests using a microindenter revealed that ibuprofen loading enhanced the mechanical strength of granules, especially above 22% drug content, which was favorable to further application of the granules as a bone defect filler

Regional differences in modelled net production and shallow remineralization in the North Atlantic subtropical gyre

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 9 (2012): 2831-2846, doi:10.5194/bg-9-2831-2012.We used 5-yr concomitant data of tracer distribution from the BATS (Bermuda Time-series Study) and ESTOC (European Station for Time-Series in the Ocean, Canary Islands) sites to build a 1-D tracer model conservation including horizontal advection, and then compute net production and shallow remineralization rates for both sites. Our main goal was to verify if differences in these rates are consistent with the lower export rates of particulate organic carbon observed at ESTOC. Net production rates computed below the mixed layer to 110 m from April to December for oxygen, dissolved inorganic carbon and nitrate at BATS (1.34±0.79 mol O2 m−2, −1.73±0.52 mol C m−2 and −125±36 mmol N m−2) were slightly higher for oxygen and carbon compared to ESTOC (1.03±0.62 mol O2 m−2, −1.42±0.30 mol C m−2 and −213±56 mmol N m−2), although the differences were not statistically significant. Shallow remineralization rates between 110 and 250 m computed at ESTOC (−3.9±1.0 mol O2 m−2, 1.53±0.43 mol C m−2 and 38±155 mmol N m−2) were statistically higher for oxygen compared to BATS (−1.81±0.37 mol O2 m−2, 1.52±0.30 mol C m−2 and 147±43 mmol N m−2). The lateral advective flux divergence of tracers, which was more significant at ESTOC, was responsible for the differences in estimated oxygen remineralization rates between both stations. According to these results, the differences in net production and shallow remineralization cannot fully explain the differences in the flux of sinking organic matter observed between both stations, suggesting an additional consumption of non-sinking organic matter at ESTOC.B. Mourino was supported by the Ramon y Cajal program from the Spanish Minister of Science and Technology. Funding for this study was provided by the Xunta de Galicia under the research project VARITROP (09MDS001312PR, PI B. Mourino) and by the Ministerio de Ciencia e Innovation MOMAC project (CTM2008-05914/MAR)

Factors controlling the community structure of picoplankton in contrasting marine environments

The effect of inorganic nutrients on planktonic assemblages has traditionally relied on concentrations rather than estimates of nutrient supply. We combined a novel dataset of hydrographic properties, turbulent mixing, nutrient concentration, and picoplankton community composition with the aims of (i) quantifying the role of temperature, light, and nitrate fluxes as factors controlling the distribution of autotrophic and heterotrophic picoplankton subgroups, as determined by flow cytometry, and (ii) describing the ecological niches of the various components of the picoplankton community. Data were collected at 97 stations in the Atlantic Ocean, including tropical and subtropical open-ocean waters, the northwestern Mediterranean Sea, and the Galician coastal upwelling system of the northwest Iberian Peninsula. A generalized additive model (GAM) approach was used to predict depth-integrated biomass of each picoplankton subgroup based on three niche predictors: sea surface temperature, averaged daily surface irradiance, and the transport of nitrate into the euphotic zone, through both diffusion and advection. In addition, niche overlap among different picoplankton subgroups was computed using nonparametric kernel density functions. Temperature and nitrate supply were more relevant than light in predicting the biomass of most picoplankton subgroups, except for Prochlorococcus and low-nucleic-acid (LNA) prokaryotes, for which irradiance also played a significant role. Nitrate supply was the only factor that allowed the distinction among the ecological niches of all autotrophic and heterotrophic picoplankton subgroups. Prochlorococcus and LNA prokaryotes were more abundant in warmer waters ( \u3e 20°C) where the nitrate fluxes were low, whereas Synechococcus and high-nucleic-acid (HNA) prokaryotes prevailed mainly in cooler environments characterized by intermediate or high levels of nitrate supply. Finally, the niche of picoeukaryotes was defined by low temperatures and high nitrate supply. These results support the key role of nitrate supply, as it not only promotes the growth of large phytoplankton, but it also controls the structure of marine picoplankton communities

Dinamización docente: las tutorías colectivas para optimizar la interacción profesor-alumno

Las tutorías colectivas, presenciales y semipresenciales, constituyen un recurso docente muy valioso para optimizar la interacción profesor-alumno. Además fomentan la igualdad e inclusión de los alumnos al realizarse en grupos reducidos

Earth and Terrestrial Planet Formation

The growth and composition of Earth is a direct consequence of planet formation throughout the Solar System. We discuss the known history of the Solar System, the proposed stages of growth and how the early stages of planet formation may be dominated by pebble growth processes. Pebbles are small bodies whose strong interactions with the nebula gas lead to remarkable new accretion mechanisms for the formation of planetesimals and the growth of planetary embryos. Many of the popular models for the later stages of planet formation are presented. The classical models with the giant planets on fixed orbits are not consistent with the known history of the Solar System, fail to create a high Earth/Mars mass ratio, and, in many cases, are also internally inconsistent. The successful Grand Tack model creates a small Mars, a wet Earth, a realistic asteroid belt and the mass-orbit structure of the terrestrial planets. In the Grand Tack scenario, growth curves for Earth most closely match a Weibull model. The feeding zones, which determine the compositions of Earth and Venus follow a particular pattern determined by Jupiter, while the feeding zones of Mars and Theia, the last giant impactor on Earth, appear to randomly sample the terrestrial disk. The late accreted mass samples the disk nearly evenly.Comment: Accepted for publication in Early Earth an AGU Monograph edited by James Badro and Michael J. Walte

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients

ObjectivesTo evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).MethodsMulticentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year.ResultsWe studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6 +/- 11.7 years. The IMID included were: spondyloarthritis (n=43), Behcet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1),ConclusionsCZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development

Texto para discussão n. 02: federalismo e transferências obrigatórias: uma discussão prospectiva sobre a distribuição do Fundo de Participação dos Estados – FPE

Este estudo tem o objetivo de discutir a atual forma de distribuição do FPE - que, conforme o STF, vigorará somente até 2012-, principalmente quanto à possibilidade de gerar um incentivo adverso para alguns estados em relação à arrecadação de impostos. Para isso, o presente trabalho apresenta uma taxonomia das transferências e os incentivos criados por elas e, com base em duas experiências internacionais – a canadense e a australiana, sugere alguns modelos para o futuro FPE, apresentando suas vantagens e desvantagens em relação a quatro hipóteses desejáveis – desvinculação da arrecadação federal, não geração de perdas financeiras aos estados, facilidade para calcular e criação de um incentivo ao crescimento da arrecadação estadual e, ainda, seu desempenho em relação ao IDH estadual de 2009.29 páginasOrçamento e FinançasPolíticas Econômica