Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.National Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011

Clinical, Molecular Characterization and Long-Term Follow-Up of a Patient with Neonatal Severe Hyperparathyroidism

Heterozygous inactivating pathogenic variants of the calcium-sensing receptor encoding gene cause autosomal dominant familial hypocalciuric hypercalcemia, whereas mutations that inactivate both alleles cause neonatal severe hyperparathyroidism, a rare and potentially fatal disease. We present the clinical and genetic characterization of a Portuguese family with familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroidism as well as the long-term follow-up of the proband. The newborn was admitted due to progressive hypotonia, feeding refusal, and dehydration. Serum calcium and parathormone levels were markedly increased. Radiological evaluation revealed osteopenia and several fractures. Total parathyroidectomy with the reimplantation of a quarter of one gland was performed. At 15 years old, she is clinically well, has normal calcium levels, and detectable parathormone values while under calcium and α-calcidiol treatment. Calcium-sensing receptor encoding gene sequencing revealed a germline homozygous nonsense pathogenic variant later confirmed as inherited.info:eu-repo/semantics/publishedVersio

Polyoxometalates as mediators in the laccase catalyzed delignification

The polyoxometalate (POM)-laccase catalytic system was applied for the first time to aerobic delignification of kraft pulps at moderate (40-60 degreesC) temperatures. Laccase was found to readily catalyze the re-oxidation of different kinds of polyoxometalates, including those, which cannot be re-oxidized by dioxygen even at high temperatures (PMo11V1, SiW11V1. etc.). This allows a sequence of catalytic redox cycles similar to that in the laccase-mediator system (LMS) where electrons are transferred from the substrate (lignin) via POM and laccase to oxygen. Results obtained showed that the POM-laccase system could decrease kappa number of eucalypt kraft pulp from 13.7 to 8.5 though the reaction rate is relatively slow. Among different POM used, SiW11V showed the best results. The effect of the process variables on the delignification was studied. The best results in delignification of eucalypt pulp were obtained at 60 degreesC, oxygen pressure of 5 bar, pH 6.3, SiW11V concentration of 4.2 mM and laccase concentration of 0.65 U/ml. The reaction temperature appears to be one of the crucial factors in the achievement of a delignification rate acceptable for practical application. (C) 2001 Elsevier Science B.V. All rights reserved

Spectroscopic on-line monitoring and stopped-flow kinetic analysis of dye degradation by laccase/mediator systems

The laccase catalyzed transformation of the acid dye Indigo Carmine (CI Acid Blue 74) was studied using various redox mediators: violuric acid (VIO), 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO), 1-hydroxybenzotriazole (HOBT), and 2,2-azinobis-(3-ethylbenzothiazoline-6-disulfonic acid diammonium salt (ABTS). Inline UV/Vis and IR spectroscopy was employed to monitor the decolorization in real-time during batch decolorization. ABTS was the most effective mediator follwed by TEMPO. Stopped flow kinetics was employed to study the initial phase of dye degradation in more detail. While the batch decolorization experiments suggested zero-order rate laws for dye transformation at an early stage, the more accurate stopped-flow kinetic experiments revealed that the rate laws for the initial phase were actually more complicated. Different pH optima for dye decolorization were found for the laccase catalyzed reaction (pH 3.5) and for the oxidation brought about by the isolated ABTS radical cation (pH 6.7)

Identification of Proteins with Potential Osteogenic Activity Present in the Water-Soluble Matrix Proteins from Crassostrea gigas Nacre Using a Proteomic Approach

Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM). We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2) were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications

Polyoxometalates as promoters of laccase-assisted reactions

A synergistic effect of polyoxometalate and laccase benzenediol:oxygen oxidoreductase, EC 1.10.3.2 has been observed in the aerobic oxidation of a hydrazonaphthalene type colorant. The considerable increase in the decolorization rate of Solophenyl Blue GL dye with the new catalytic system composed by laccase and heptamolybdopentovanadophosphate heteropolyanion, when compared with the treatment with enzyme or heteropolyanion alone, was tentatively explained by the redox mediation action of the heteropolyanion

O Índice de Resistência Microcirculação Para o Estudo Invasivo da Microcirculação Coronária. Descrição e Validação de um Modelo Animal

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status

Lesão Tumoral Primária do Pulmão em Adolescente

Primary lung tumors in the pediatric age group are rare, histologically diverse and have different therapeutic approaches. The inflammatory myofibroblastic tumor of the lung accounts for 0.04% - 1.2% of all lung tumors, is more common in children and young adults and its etiology is unknown. The diagnosis is difficult as clinical and radiological findings are highly variable. We report a case of a 15-year-old adolescent who presented with a single pulmonary nodule on a chest radiograph, in the context of a respiratory infection, and whose etiological investigation revealed an inflammatory myofibroblastic tumor of the lung. Atypical resection was performed by video-assisted thoracoscopic surgery, with full recovery. We highlight the rarity of this entity, the need for a high suspicion index and the diagnostic investigation undertaken to reach a definitive diagnosis and a successful outcome.info:eu-repo/semantics/publishedVersio

Polyoxometalate/laccase-mediated oxidative polymerization of catechol for textile dyeing

The synergistic effect between polyoxometalates (POMs), namely K5[SiW11VVO40]·11H2O and H5[PMo10 VV2O40]·13H2O and laccase from ascomycete Myceliophthora thermophila has been employed for the first time in oxidative polymerization of catechol. Such a laccase-mediator system allowed the formation of a relatively high molecular weight polycatechol as confirmed by size exclusion chromatography and electrospray ionization mass spectrometry (ESI-MS) (3990 Da when using K5[SiW11VVO40]·11H2O and 3600 Da with H5[PMo10VV 2O40]·13H2O). The synthesized polymers were applied as dyes for the dyeing of flax fabrics. The color intensity of flax fabrics colored with polymer solutions was evaluated by diffuse reflectance spectrophotometry via k/s measurements (+10% of fixation ratio). A new synthetic process allowed a dyeing polymer, provided upon flax coloration, better color fixation and color resistance when compared to that obtained by conventional synthesis with laccase solely or with addition of organic mediator (1-hydroxybenzotriazole)

Lipase-ultrasound assisted synthesis of polyesters

Poly (ethylene glutarate), poly (ethylene malonate) and poly (ethylene phthalate), were enzymatically synthesized by immobilized Candida antarctica lipase B in solvent free conditions. The synthesis of these polyesters was based on the ester-ester exchange reaction between ethylene glycol diacetate and di-ethyl glutarate, di-benzyl malonate, di-n-octyl phthalate to produce poly (ethylene glutarate), poly (ethylene malonate) and poly (ethylene phthalate), respectively. The effect of ultrasound and PET polymeric beads on the polyester synthesis was evaluated and showed to improve the synthesis of all polyesters. Ultrasound, as a green solvent-free technology, showed high potentiality for the polyester synthesis intensification.All authors gratefully acknowledge the financial support provided by International Joint Research Laboratory for Textile and Fibre Bioprocesses at Jiangnan University. The authors are also thankful to the Department of Chemical Engineering, Institute of Chemical Technology, Matunga (E), Mumbai-400019, India and to the Bioprocess and Bio nanotechnology Research Group (BBRG) of University of Minho. Authors would like also to acknowledge the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 Programa Operacional Regional do Norte and to the Fundamental Research Funds for the Central Universities (No. JUSRP51622A) 2016, Jiangsu Province Scientific Research Innovation Project for Academic Graduate Students (No. KYLX16_0788).info:eu-repo/semantics/publishedVersio