12 research outputs found
Lawsonia intracellularis proliferative enteropathy in a filly
No full textProliferative enteropathy (PE) caused by the obligate intracellular bacterium Lawsonia intracellularis is a disease of high economic impact in swine worldwide. In most other species the disease occurs as a sporadic infection. This paper reports a PE caused by L. intracellularis in a 9-month-old Pura Raza Española filly with a history of profuse diarrhoea. Pathological lesions consisted of a severe proliferative enteritis associated with argyrophilic bacteria in the apical cytoplasm of proliferating crypt epithelium. Characteristic PCR products confirmed the presumptive diagnosis of L. intracellularis infection. To our knowledge this is the first report of PE in a horse in Europe caused by L. intracellularis
Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis
No full textBACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response
Using a digital internal communication strategy for digital capability development
No full textThis study aims to illustrate the multidimensional perspective of digital internal communication defined and applied in the context of strategic communication, and how digital capability development and training are embedded. We use a conceptual approach to integrate literature from the fields of digital transformation, digital internal communication, and digital human resource capability development. The findings reveal that an organisational system’s technical (channels and platforms, and policy) and social (leadership, culture, and collaboration) digital elements are interrelated across all communication levels, contributing to digital capability development. Furthermore, digital trust is required for and enforced by effective learning in the digital space. This study proposes a holistic digital internal communication strategy focusing on developing digital human resource capabilities as a strategic training initiative in organisational settings to promote strategic communication. Hence, a strategic map for digital capability development and training offers senior leadership a practical and adaptable tool. It allows them to create their own organisation-specific digital human resource initiatives, contributing to organisational learning and trust-building as the bedrock of organisational sustainability and success
Review and Novel Formulae for Transmittance and Reflectance of Wedged Thin Films on absorbing Substrates
No full textHistorically, spectroscopic techniques have been essential for studying the optical properties of thin solid films. However, existing formulae for both normal transmission and reflection spectroscopy often rely on simplified theoretical assumptions, which may not accurately align with real-world conditions. For instance, it is common to assume (1) that the thin solid layers are deposited on completely transparent thick substrates and (2) that the film surface forms a specular plane with a relatively small wedge angle. While recent studies have addressed these assumptions separately, this work presents an integrated framework that eliminates both assumptions simultaneously. In addition, the current work presents a deep review of various formulae from the literature, each with their corresponding levels of complexity. Our review analysis highlights a critical trade-off between computational complexity and expression accuracy, where the newly developed formulae offer enhanced accuracy at the expense of increased computational time. Our user-friendly code, which includes several classical transmittance and reflectance formulae from the literature and our newly proposed expressions, is publicly available in both Python and Matlab at this link
Enhancing the Swanepoel method: precise envelope detection of thin-film transmission spectra
No full textThe Swanepoel method is a widely used optical technique for characterizing thin films through normal-incidence transmission measurements. A critical step in this approach involves extracting the upper and lower envelopes of the measured oscillatory spectrum. By analyzing the transmission spectrum and its corresponding envelopes, the Swanepoel procedure enables precise determination of the film refractive index and extinction coefficient. However, even minor inaccuracies in envelope construction can propagate significant errors into the final characterization results. To address this challenge, we present what we believe to be a novel physics-informed optimization algorithm for envelope detection. Our mathematical model reformulates the envelope detection problem as a global optimization task that enforces the physical properties of the Swanepoel envelopes. Extensive validation on fifty randomly generated transmission spectra demonstrates unprecedented accuracy: the method achieves root-mean-square errors (RMSE) below 0.10% for the upper envelope and 0.06% for the lower envelope (more than doubling the accuracy of current state-of-the-art approaches). Furthermore, the proposed model has been assessed with two experimental transmission spectra, demonstrating its robustness and accuracy with real noisy data. We have developed an open-source Python software package (see text below). This software includes not only our innovative envelope construction algorithm but also additional envelope drawing algorithms for comparison and an efficient implementation of the Swanepoel method, enabling complete optical characterization of thin films
Degradation Of Dipyrone By The Electro-fenton Process In An Electrochemical Flow Reactor With A Modified Gas Diffusion Electrode
No full textThe increasing occurrence of antibiotics and their metabolites in surface and ground waters is causing a significant impact on the environment and needing of developing novel treatments for the complete removal of such contaminants. This paper presents the study of the electrogeneration of hydrogen peroxide (H2O2) in acidic medium and the degradation of the analgesic dipyrone in an electrochemical flow reactor using a gas diffusion electrode (GDE) modified with 5.0% cobalt (II) phthalocyanine (CoPc) and pressurized with O2. The highest yield of H2O2(133 mg L-1) was achieved after 90 min of electrolysis at an applied potential of -2.1 V (vs. Pt//Ag/AgCl/KCls) and the best results for degradation of dipyrone were obtained under electro-Fenton conditions, where the total organic carbon (TOC) was reduced 62.8% after 90 min of reaction and 49.1 kW h of energy was consumed per kg of dipyrone degraded.25916731680Joss, A., Zabczynski, S., Gobel, A., Hoffmann, B., Loffler, D., McArdell, C.S., Ternes, T.A., Siegrist, H., (2006) Water Res., 40, p. 1686Carballa, M., Omil, F., Ternes, T., Lema, J.M., (2007) Water Res., 41, p. 2139Bila, D.M., Dezotti, M., (2003) Quim. Nova, 26, p. 523Tauxe-Wuersch, A., De Alencastro, L.F., Grandjean, D., Tarradellas, J., (2005) Water Res., 39, p. 1761Kasprzyk-Hordern, B., Dinsdale, R.M., Guwy, A.J., (2008) Water Res., 42, p. 3498Al Aukidy, M., Verlicchi, P., Jelic, A., Petrovic, M., Barcelò, D., (2012) Sci. Total Environ., 438, p. 15Martínez Bueno, M.J., Hernando, M.D., Herrera, S., Gómez, M.J., Fernández-Alba, A.R., Bustamante, I., García-Calvo, E., (2010) Int. J. Environ. Anal. Chem., 90, p. 321Vystavna, Y., Huneau, F., Grynenko, V., Vergeles, Y., Celle-Jeanton, H., Tapie, N., Budzinski, H., Le Coustumer, P., (2012) Water, Air, Soil Pollut., 223, p. 2111Nikolaou, A., Meric, S., Fatta, D., (2007) Anal. Bioanal. Chem., 387, p. 1225Zylber-Katz, E., Granit, L., Levy, M., (1992) Eur. J. Clin. Pharmacol., 42, p. 187Arkhipchuk, V.V., Goncharuk, V.V., Chernykh, V.P., Maloshtan, L.N., Gritsenko, I.S., (2004) J. Appl. Toxicol., 24, p. 401Wiegel, S., Aulinger, A., Brockmeyer, R., Harms, H., Loffler, J., Reincke, H., Schmidt, R., Wanke, A., (2004) Chemosphere, 57, p. 107Fent, K., Weston, A.A., Caminada, D., (2006) Aquat. Toxicol., 76, p. 122Gomez, M.J., Martinez Bueno, M.J., Lacorte, S., Fernandez-Alba, A.R., Aguera, A., (2007) Chemosphere, 66, p. 993Nikolova, I., Tencheva, J., Voinikov, J., Petkova, V., Benbasat, N., Danchev, N., (2012) Biotechnol. Biotechnol. Equip., 26, p. 3329Gomez, M.J., Sirtori, C., Mezcua, M., Fernandez-Alba, A.R., Aguera, A., (2008) Water Res., 42, p. 2698Reis, R.M., Baio, J.A.F., Migliorini, F.L., Rocha, R.S., Baldan, M.R., Ferreira, N.G., Lanza, M.R.V., (2013) J. Electroanal. Chem., 690, p. 89Huang, C.P., Dong, C., Tang, Z., (1993) Waste Manage., 13, p. 361Neyens, E., Baeyens, J., (2003) J. Hazard Mater., 98, p. 35Mininni, G., Sbrilli, A., Guerriero, G., Rotatori, M., (2004) Chemosphere, 54, p. 1337Beati, A.A.G.F., Rocha, R.S., Oliveira, J.G., Lanza, M.R.V., (2009) Quim. Nova, 32, p. 125Rocha, R.S., Beati, A.A.G.F., Oliveira, J.G., Lanza, M.R.V., (2009) Quim. Nova, 32, p. 354Assumpc¸ão, M.H.M.T., Moraes, A., De Souza, R.F.B., Gaubeur, I., Oliveira, R.T.S., Antonin, V.S., Malpass, G.R.P., Santos, M.C., (2012) Appl. Catal.-A: Gen., 411-412, p. 1Reis, R.M., Beati, A.A.G.F., Rocha, R.S., Assumpc¸ão, M.H.M.T., Santos, M.C., Bertazzoli, R., Lanza, M.R.V., (2012) Ind. Eng. Chem. Res., 51, p. 649Yeager, E., (1984) Electrochim. Acta, 29, p. 1527Kinoshita, K., (1988) Carbon: Electrochemical and Physicochemical Properties, , Wiley: New York, USALipkowski, J., Ross, P., (2008) Electrocatalysis, , Wiley-VCH: New York, USACordeiro, G.S., Rocha, R.S., Valim, R.B., Migliorini, F.L., Baldan, M.R., Lanza, M.R.V., Ferreira, N.G., (2013) Diamond Relat. Mater., 32, p. 54Rocha, R.S., Reis, R.M., Beati, A.A.G.F., Sotomayor, M.D.P.T., Bertazzoli, R., Lanza, M.R.V., (2012) Quim. Nova, 35, p. 1961Barros, W.R.P., Reis, R.M., Rocha, R.S., Lanza, M.R.V., (2013) Electrochim. Acta, 104, p. 12Beati, A.A.G.F., Reis, R.M., Rocha, R.S., Lanza, M.R.V., (2012) Ind. Eng. Chem. Res., 51, p. 5367Rezende, L.G.P., Prado, V.M., Rocha, R.S., Beati, A.A.G.F., Sotomayor, M.D.P.T., Lanza, M.R.V., (2010) Quim. Nova, 33, p. 1088Ikehata, K., Naghashkar, N.J., El-Din, M.G., (2006) Ozone: Sci. Eng., 28, p. 353Fan, Y., Ai, Z., Zhang, L., (2010) J. Hazard Mater., 176, p. 678Poyatos, J.M., Muñio, M.M., Almecija, M.C., Torres, J.C., Hontoria, E., Osorio, F., (2010) Water, Air, Soil Pollut., 205, p. 187Giri, A.S., Golder, A.K., (2014) Ind. Eng. Chem. Res., 53, p. 1351Assumpc¸ão, M.H.M.T., Moraes, A., De Souza, R.F.B., Reis, R.M., Rocha, R.S., Gaubeur, I., Calegaro, M.L., Santos, M.C., (2013) Appl. Catal.-A: Gen., 462-463, p. 25
Remoção de fármacos e avaliação de seus produtos de degradação através de tecnologias avançadas de tratamento
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Química.A ocorrência de fármacos no meio ambiente tem se tornado um assunto de interesse nos últimos anos. Grande número desses compostos têm sido detectados em efluentes de estações de tratamento de esgoto (ETEs) municipais, águas superficiais e, menos frequentemente, em águas subterrâneas e água potável em todo o mundo. Alguns dos efeitos adversos causados por fármacos incluem toxicidade aquática, desenvolvimento de resistência em bactérias patogênicas, genotoxicidade, e desregulação endócrina. Diferentes fontes podem ser indicadas para explicar o aparecimento de fármacos no ambiente aquático. Atualmente, é amplamente reconhecido que a principal fonte de poluição são os efluentes de ETEs. Portanto, o descarte de resíduos farmacêuticos nos efluentes de ETEs deve ser minimizado o máximo possível. A remoção de poluentes orgânicos recalcitrantes como fármacos na água e em efluentes pode ser obtida utilizando tecnologias avançadas de tratamento, tais como bioreatores com membranas (BRMs), processos oxidativos avançados (POAs) e adsorção em carvão ativado. O objetivo deste trabalho é avaliar a eficiência de remoção de fármacos por meio de BRMs de ultrafiltração, POAs e adsorção em carvão ativado, identificar metabólitos ou produtos de degradação de fármacos originados durante os tratamentos bem como realizar um estudo cinético de degradação desses compostos. Os fármacos usados neste estudo, três antiinflamatórios não-esteroidais (AINEs) (acetaminofeno, cetoprofeno e naproxeno) e três antibióticos (roxitromicina, sulfametoxazol e trimetoprima), foram adquiridos da Sigma-Aldrich. A primeira etapa do trabalho consistiu em utilizar dois BRMs, com idade de lodo de 15 (BRM-15) e 30 (BRM-30) dias, para avaliar a degradação dos fármacos adicionados no efluente proveniente do tanque de equalização da estação de tratamento de esgoto doméstico (ETE) da cidade de Aachen (Alemanha), que servia de alimentação para os BRMs. Os fármacos foram adicionados diariamente numa concentração de 50 µg/L/d em cada BRM, durante aproximadamente quatro semanas. Em uma segunda etapa de trabalho, compostos farmacêuticos dissolvidos em água Milli-Q ou no permeado dos BRMs a uma concentração de 100 µg/L foram tratados por POAs. Os tratamentos por meio de POAs (radiação UV, O3, H2O2/UV, Fenton e foto-Fenton) foram realizados em um reator cilíndrico de vidro (500 mL) ao longo de 30 minutos. A radiação UV foi proporcionada por uma lâmpada a vapor de mercúrio de média pressão de 15 W. A agitação do sistema foi proporcionada pelo uso de um agitador magnético. Sulfato ferroso heptahidratado foi utilizado como fonte de íons de ferro para o processo Fenton e foto-Fenton. A determinação e a quantificação dos fármacos e seus metabólitos, presentes no permeado dos BRMs, e dos produtos de degradação, originados durante o tratamento por POAs, foram realizadas por meio de um sistema de cromatografia líquida acoplado a um sistema de espectrometria de massa (LC-MS) e espectrometria tandem de massa (LC-MSn), aplicando ionização por electrospray nos modos positivo (IES(+)) (para acetaminofeno, roxitromicina, sulfametoxazol e trimetoprima) e negativo (IES(-)) (para cetoprofeno e naproxeno). Em uma terceira etapa de trabalho, avaliou-se a eficiência de remoção dos fármacos em solução aquosa por meio de adsorção em carvão ativado. Soluções aquosas de fármacos (300 mL) com diferentes concentrações iniciais (1-10 mg/L) foram colocadas em contato com diferentes dosagens de carvão ativado (1; 1,5; 2; 2,5, 3 g/L) por 6h a 25oC, e a concentração dos fármacos foi determinada usando um espectrofotômetro UV-vis. Com relação aos resultados obtidos por meio do tratamento por BRMs, observou-se que os AINEs foram removidos com maior eficiência do que os antibióticos para ambos os BRMs e quando se comparou a eficiência de remoção média entre os dois BRMs, observou-se que o BRM-30 apresentou uma eficiência de remoção maior para todos os compostos em relação ao BRM-15. Metabólitos de acetaminofeno, cetoprofeno e naproxeno foram identificados no permeado de ambos os BRMs. Com relação aos resultados obtidos pelo tratamento utilizando POAs, os compostos cetoprofeno e sulfametoxazol mostraram-se bastante sensíveis à radiação UV. Apesar do tratamento com O3 ter apresentado as maiores eficiências de remoção, não se pôde concluir que foi o melhor tratamento, uma vez que apresentou produtos de degradação desconhecidos cuja polaridade e toxicidade não foram avaliadas. Com relação aos resultados obtidos por adsorção em carvão ativado, observou-se uma eficiência de remoção maior do que 90% para todos os compostos. A adsorção dos compostos alcançou estado de equilíbrio após 6h e foi descrita por meio do uso de isotermas lineares. A cinética de adsorção dos fármacos foi discutida usando 3 modelos cinéticos e verificou-se que o modelo cinético de pseudo-segunda ordem pode descrever a adsorção dos fármacos sobre o carvão ativado
Desenvolvimento de metodologias analíticas para determinação de fármacos em fluidos biológicos e amostras ambientais por cromatografia líquida e gasosa
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química.Neste trabalho está apresentada a análise de fluído biológico e matriz ambiental para a determinação de fármacos, avaliando etapas distintas das metodologias analíticas. Na determinação de paracetamol e hidroclorotiazida em urina, buscou-se enfatizar o método de quantificação. A determinação foi realizada pelas técnicas convencionais de padronização por padrão externo e adição do analito e pelo método proposto de padronização por adição. A técnica proposta não apresentou diferença quando avaliada estatisticamente. Para a determinação de fármacos em matriz ambiental, foi dada ênfase ao desenvolvimento e otimização de metodologias, utilizando a extração em fase sólida (SPE) e microextração em fase sólida (SPME). Primeiramente, foi otimizada univariavelmente e validada metodologia visando à extração de paracetamol, AAS, diclofenaco e carbamazepina de amostras de água por SPE e cromatografia líquida. A metodologia otimizada apresentou boa linearidade e valores de recuperação aceitáveis. Enfim, uma metodologia para a determinação simultânea de fármacos ácidos (ibuprofeno, fenoprofeno e diclofenaco) e básicos (diazepam e loratadina) em água através da SPME e cromatografia gasosa foi desenvolvida. Aplicou-se as ferramentas multivariadas para otimização. A metodologia proposta foi comparada a metodologias onde cada classe de fármaco era extraída separadamente e mostrou-se muito eficiente
In pursuit of a novel UTI treatment strategy - an "in silico" study of the FimH adhesin
No full textCarbohydrate-binding proteins (particularly lectins) are frequent targets of
present pharmaceutical research. While of high priority due to their involvement
in an array of pathophysiological events, these systems (along with their
saccharidic ligands) present many challenges related, in part, to the limited
means of their in-depth structural exploration. A foothold towards improving the
design throughput of carbohydrate-based drugs is provided by the
state-of-the-art in silico technologies, offering both means of structure
generation and refinement as well as rapid screening of putative ligands. In
this account, the application of some of these methods (docking, molecular
dynamics, and MM-GBSA/QSAR protocols), toward inhibiting FimH - a virulence
factor of urinary tract infections - is presented. The role of this bacterial
lectin involves the adhesion to highly-mannosylated urothelial cell surfaces.
This process is supported by the presence of urine flow, lead- ing to the
so-called catch-bonding characteristics. The presented work was focused
primarily on the rationalization and optimization of the binding of mannosidic
ligands with available crystallographic and in vitro data. As a result,
several series of new promising compounds were designed, with selected among
them synthesized, assayed, and published. In addition, an array of molecular
dynamics simulation techniques was employed to probe the structural properties
of the native, two-domain protein in presence and absence of shear conditions.
Through this, a receptor conformation was identified, that differed (including
the binding site) from ones previously employed in structure-based design
approaches. Given the wealth of data reporting the existence of FimH variants
with a broad range of affinities towards their natural ligands (further
dependent on many endogenic and exogenic factors), the reported discoveries may
lead to versatile and potent inhibitors, superior to currently applied
antibiotic treatments
Integrated testing strategy for the study of the effects of the human pharmaceutical dutasteride on fish
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.In recent years, a growing number of human pharmaceuticals have been detected in the aquatic environment, generally at low concentrations (sub-ng/L to low μg/L). These compounds are characterised by highly specific mechanisms of action, high potency and prolonged activity in order to minimise dosing requirements and potential toxicity in patients. Among the various classes of pharmaceuticals, steroids and anti-steroids are widely used, as shown by the analysis of their clinical use carried out at the beginning of this Ph.D. project. Although the amounts used are much lower than the amounts of some other pharmaceuticals (e.g. analgesics), their ability to affect important physiological processes in fish (e.g. reproduction) at very low concentrations (ng/L) suggest that this class of compounds should represent a high priority for ecotoxicological research. In particular, this Ph.D. project addressed the question of whether or not dutasteride, a human pharmaceutical mainly used to treat benign prostatic hyperplasia, may cause adverse effects in the teleost fathead minnow (Pimephales promelas) by inhibiting the activity of both isoforms of 5α-reductase (5αR), the enzyme which convert testosterone into dihydrotestosterone (DHT). The theoretical framework used to guide the design of the experimental studies was based on the combination of several conceptual approaches, including the study of the evolutionary degree of conservation and functionality of the drug target in non-target species, and the cross-species extrapolation of pharmacological and toxicological information generated during pre-clinical and clinical studies in mammals during drug development. The results obtained during the first phase of this Ph.D. project strongly suggested that DHT has a physiological role in the fathead minnow. In fact, 5αRs are evolutionary conserved in this species, 5αRs genes are expressed in tissues such as the testis, and DHT circulates in fathead minnow plasma at concentrations similar to those detected in humans. These findings represented the rationale for testing the effects of dutasteride in the fathead minnow. Dutasteride caused significant adverse effects in all the in vivo studies performed in order to evaluate its potential toxicity on fish, including early life stage and short term reproduction studies, and all the tested life stages were sensitive to the inhibition of 5αRs activity; however, none of the observed adverse effects occurred at concentrations of exposure lower than 32 μg/L (measured concentration). The results also showed that female fish are highly sensitive to disruption of the androgenic pathways, highlighting their utility for the evaluation of potential adverse effects caused by anti-androgens on fish. In conclusion, the results presented in this Thesis suggest that, at present, the potential presence of dutasteride in the environment does not represent a risk to wild fish populations, due to the high concentrations required to elict significant adverse effect (LOEC = 32 μg/L) and the low volume of drug prescribed every year (5.07 kg in UK in 2006). However, the high bioaccumulation factor of dutasteride suggest that further studies should be conducted to elucidate the role played by the bioaccumulation process in the toxicity responses observed in fish.This work is funded by GlaxoSmithKlin
