Changes in bone Pb accumulation: Cause and effect of altered bone turnover

Notice: this is the author’s version of a work that was accepted for publication in Bone. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bone, [Vol 64 (2014 Jul)] DOI 10.1016/j.bone.2014.04.021"This paper assesses the magnitude of Pb uptake in cortical and trabecular bones in healthy animals and animals with altered balance in bone turnover, and the impact of exposure to Pb on serum markers of bone formation and resorption. The results reported herein provide physiological evidence that Pb distributes differently in central compartments in Pb metabolism, such as cortical and trabecular bone, in healthy animals and animals with altered balance in bone turnover, and that exposure to Pb does have an impact on bone resorption resulting in OC-dependent osteopenia. These findings show that Pb may play a role in the etiology of osteoporosis and that its concentration in bones varies as a result of altered bone turnover characteristic of this disease, a long standing question in the field. In addition, data collected in this study are consistent with previous observations of increased half-life of Pb in bone at higher exposures. This evidence is relevant for the necessary revision of current physiologically based kinetic models for Pb in humans.

The implementation of radiation technology program in Portugal

The development of ionizing radiation pplications for Industrial purposes in Portugal began near of 1982 with the support of IAEA. The main steps to put forward prior to the implementation were the sitting and the design study in order to build up the facility. Subsequently, the main parameters to be achieved were the construction, the commissioning, the operation, the maintenance and the foreseen decommission. Once a quality system for the gamma facility was established, the following stage is to develop, validate and control the terilization/disinfection process. The research activities carried out in the UTR have been closely related with the main applications of this technology namely, the sterilization of medical devices and pharmaceuticals and other products’ decontamination. Recently, a research Cobalt-60 equipment was upgraded and a LINAC was implemented in order to sustain the R&D. Fundamental and development research is ngoing in order to understand the irradiation mechanisms of action and to apply the technology with safety and quality patterns.The first author would like to thank Gulbenkian Foundation in Portugal and NIC2010 the financial support for the opportunity to participate at NAARRI International Conference

"Detachment of the carinal hook following endobronchial intubation with a double lumen tube"

<p>Abstract</p> <p>Background</p> <p>Carinal hooks increases difficulty at endotracheal intubation. Amputation of the carinal hook during passage and malpositioning of the tube to the hook are some of the potential problems related with left-sided Carlens double lumen tube (DLT). This article reports an amputation of the hook during a difficult selective intubation and aimed at calling the attention to complications associated with DLTs and the importance of fiberoptic bronchoscopy.</p> <p>Case presentation</p> <p>A 68 year-old woman was scheduled for right-sided thoracotomy in whom blind DLT insertion was performed. Narrowed trachea causes difficulty in rotating the DLT 90° counter-clockwise. After carinal hook was noticed upon visual inspection of the DLT, fiberoptic bronchoscopy was used to remove the missing part (with the use of forceps) from the right mainstem bronchus.</p> <p>Conclusion</p> <p>Insertion of DLTs with carinal hook is associated with technical problems and potentially life-threatening hazards have discouraged their use. Fiberoptic evaluation and repositioning solves most of the problems. Although amputation of the carinal hook has not been previously reported, clinicians should be alert. This case report emphasizes the utility of the fiberoptic bronchoscopy in the operating theatre for placement, positioning and inspection of the carinal hook DLT.</p

Harmine and Piperlongumine Revert TRIB2-Mediated Drug Resistance.

Therapy resistance is responsible for most relapses in patients with cancer and is the major challenge to improving the clinical outcome. The pseudokinase Tribbles homologue 2 (TRIB2) has been characterized as an important driver of resistance to several anti-cancer drugs, including the dual ATP-competitive PI3K and mTOR inhibitor dactolisib (BEZ235). TRIB2 promotes AKT activity, leading to the inactivation of FOXO transcription factors, which are known to mediate the cell response to antitumor drugs. To characterize the downstream events of TRIB2 activity, we analyzed the gene expression profiles of isogenic cell lines with different TRIB2 statuses by RNA sequencing. Using a connectivity map-based computational approach, we identified drug-induced gene-expression profiles that invert the TRIB2-associated expression profile. In particular, the natural alkaloids harmine and piperlongumine not only produced inverse gene expression profiles but also synergistically increased BEZ235-induced cell toxicity. Importantly, both agents promote FOXO nuclear translocation without interfering with the nuclear export machinery and induce the transcription of FOXO target genes. Our results highlight the great potential of this approach for drug repurposing and suggest that harmine and piperlongumine or similar compounds might be useful in the clinic to overcome TRIB2-mediated therapy resistance in cancer patients.This work was supported by the FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA (FCT) Research Center Grant UID/BIM/04773/2013, Centre for Biomedical Research (CBMR), and by the Spanish Ministry of Science, Innovation and Universities through Grant RTI2018-094629-B-I00 to WL. B.I.F. was supported by FCT-SFRH/BPD/100434/2014 and the Marie Curie Individual Fellowship project TRIBBLES (#748585). This work was also supported by two LPCC-NRS/Terry Fox grants (2016/2017; 2017/2018). S. Machado is the recipient of a ProRegeM grant PD/BD/114258/2016. I. Duarte was supported by a scholarship from FCT Grant PTDC/BEX-BID/5410/2014S

Advanced polymeric membranes as biomaterials based on marine sources envisaging the regeneration of human tissues

The self-repair capacity of human tissue is limited, motivating the arising of tissue engineering (TE) in building temporary scaffolds that envisage the regeneration of human tissues, including articular cartilage. However, despite the large number of preclinical data available, current therapies are not yet capable of fully restoring the entire healthy structure and function on this tissue when significantly damaged. For this reason, new biomaterial approaches are needed, and the present work proposes the development and characterization of innovative polymeric membranes formed by blending marine origin polymers, in a chemical free cross-linking approach, as biomaterials for tissue regeneration. The results confirmed the production of polyelectrolyte complexes molded as membranes, with structural stability resulting from natural intermolecular interactions between the marine biopolymers collagen, chitosan and fucoidan. Furthermore, the polymeric membranes presented adequate swelling ability without compromising cohesiveness (between 300 and 600%), appropriate surface properties, revealing mechanical properties similar to native articular cartilage. From the different formulations studied, the ones performing better were the ones produced with 3 % shark collagen, 3% chitosan and 10% fucoidan, as well as with 5% jellyfish collagen, 3% shark collagen, 3% chitosan and 10% fucoidan. Overall, the novel marine polymeric membranes demonstrated to have promising chemical, and physical properties for tissue engineering approaches, namely as thin biomaterial that can be applied over the damaged articular cartilage aiming its regeneration.The authors would like to acknowledge the Portuguese Foundation of Science and Technology (FCT) for Ph.D. fellowship (D. N. Carvalho, under the scope of doctoral program TERM&SC, ref. PD/BD/143044/2018), post-doctoral fellowship (L.C. Rodrigues, ref. SFRH/BPD/93697/2013) and research project with ref. PTDC/CTM-CTM/29813/2017-(POCI-01-0145-FEDER-029813). The authors also thank Jellagen Ltd. (UK) for the provision of purified jellyfish collagen and Julio Maroto (Fundación CETMAR, Vigo, Spain) for the kind offer of the squid pens for chitosan production.This work has been partially funded by ERDF under the scope of the Atlantic Area Program through project EAPA_151/2016 (BLUEHUMAN)

Chemical composition and antibacterial activity of essential oils from the medicinal plant Mentha cervina L. grown in Portugal

Mentha cervina is a medicinal plant traditionally used in Portugal in folk medicine, in different gastric disorders and inflammations of the respiratory tract. In order to validate those traditional uses, M. cervina essential oils (EOs) were characterized by GC and GC–MS and their antimicrobial activity was tested against 23 bacterial strains (including multiresistant strains). The EOs were dominated by the monoterpenes pulegone (52–75%), isomenthone (8–24%), limonene (4–6%), and menthone (1–2%). The antibacterial activity of these EOs was compared to that of the main components standards. The most effective antibacterial activity was expressed by the EOs against the Gram-negative bacteria, Escherichia coli and Acinetobacter baumanni, with MIC values of 1 mg/ml. The EOs complex mixtures were more active than the individual aromatic components supporting the hypothesis that the EOs antibacterial activity is a function of the synergistic effect of their different aromatic components. These results show the potential role of M. cervina EOs as antibacterial agents and validate the traditional use of this plant

uma nova ferramenta de vigilância transnacional da tuberculose no espaço lusófono

A Tuberculose (TB) permanece um grave problema de saúde pública na Comunidade dos Países de Língua Portuguesa (CPLP). Apesar da ampla variância da incidência da TB nos seus estados-membro e de um fluxo migratório contínuo entre os países que integram este grupo, existe uma enorme lacuna no que diz respeito ao conhecimento da estrutura populacional conjunta do Mycobacterium tuberculosis e circulação de estirpes entre estes países. Para fazer face a esta necessidade, foi agregado e analisado o maior conjunto de dados respeitante à diversidade genotípica e resistência fenotípica na CPLP que compreende um total de 1447 isolados clínicos, incluindo 423 isolados multirresistentes de cinco países da CPLP. Por forma a tornar estes dados disponíveis para a comunidade científica e autoridades de saúde pública, foi desenvolvida a CPLP-TB (disponível em http://cplp-tb.ff.ulisboa.pt), uma base de dados disponível online e provida de aplicativos para análise exploratória do conteúdo. Como ferramenta de saúde pública, espera-se que venha a contribuir para um conhecimento mais aprofundado da estrutura populacional do M. tuberculosis e circulação de estirpes na CPLP de forma a apoiar a avaliação de risco e tendências específicas para diversos clones. Tuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analyzed the largest CPLP M . tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries. To make this data available to the scientific community and public health authorities we developed CPLP-TB (available at http://cplp-tb.ff.ulisboa.pt), an online database coupled with web-based tools for exploratory data analysis. As a public health tool, it is expected to contribute to improved knowledge on the M. tuberculosis population structure and strain circulation within the CPLP, thus supporting the risk assessment of strain-specific trends.publishersversionpublishe