In vitro glucuronidation of kaempferol and quercetin by human UGT-1A9 microsomes

AbstractFlavonoids are important polyphenolic substances with widespread occurrence in plants and therefore in the human diet. Although considerable work has been done on the pharmacology of flavonoids, the understanding of their metabolism is still incomplete. In this work, the in vitro glucuronidation of the common dietary flavonoids quercetin and kaempferol by human UDP-glucuronosyltransferase microsomes (UGT-1A9) was investigated using HPLC and LC–MS. The two flavonoids were extensively metabolised by this enzyme with four monoglucuronides of quercetin and two of kaempferol being detected after incubation. The presence of a quercetin monoglucuronide in the urine of a volunteer after consumption of Ginkgo biloba tablets was demonstrated

Modelling coordination in biological systems

We present an application of the Reo coordination paradigm to provide a compositional formal model for describing and reasoning about the behaviour of biological systems, such as regulatory gene networks. Reo governs the interaction and flow of data between components by allowing the construction of connector circuits which have a precise formal semantics. When applied to systems biology, the result is a graphical model, which is comprehensible, mathematically precise, and flexibl

Prevalência de fatores de risco coronariano em praticantes de futebol recreacional

Verificar a prevalência dos fatores de risco coronariano em praticantes de futebol recreacional e comparar o risco coronariano de acordo com a faixa etária. Avaliaram- se 201 homens que praticavam futebol recreacionalmente, com idade média de 25.3 ± 6.0 anos. Todos responderam ao questionário RISKO, que é um questionário contendo 8 fatores de risco, sendo o risco coronariano representado pela soma dos escores obtidos nos 8 fatores de risco. O tratamento estatístico constou da exploração descritiva e da ANOVA oneway, com post hoc Tuckey, para comparação entre as faixas etárias. Adotou- se um nível de significância de p < 0.05. O escore médio de risco coronariano encontrado foi de 18.22 ± 3.49 pontos (12- 29 pontos), classificado como risco médio. Em relação às faixas etárias o risco coronariano médio obtido foi de: 16.58 ± 3.11 pontos para os indivíduos entre 18- 20 anos; 18.21 ± 3.08 pontos para aqueles entre 21- 30 anos; 20.58 ± 3.89 pontos para os sujeitos entre 31- 40 anos; e 21.00 ± 4.53 para aqueles com idade superior a 40 anos. Em relação a cada fator de risco isoladamente, as prevalências observadas, em ordem decrescente, foram: excesso de peso (44.78%), sedentarismo (38.31%), hipercolesterolemia (24.38%), tabagismo (17.41%), hereditariedade (12.94%) e hipertensão (8.46%). Os fatores de risco coronariano mais prevalentes nos praticantes de futebol recreacional foram o excesso de peso, o sedentarismo e a hipercolesterolemia, apresentando classificação de risco médio e crescimento com o aumento da idade, sobretudo após os 31 anos.Investigar la prevalencia de factores de riesgo coronario en jugadores recreacionales de fútbol y comparar el riesgo coronario según grupo de edad. Métodos: Se evaluaron 201 hombres que practicaban fútbol de forma recreativa, con edad media de 25.3 ± 6.0 años. Todos respondieron el cuestionario RISKO, que contiene 8 factores de riesgo y representándose el riesgo coronario por la suma de las puntuaciones obtenidas en los 8 factores. El análisis estadístico incluyó descripción de los datos y ANOVA one way, con post hoc Tukey, para comparaciones entre grupos de edad, con nivel de significación de p < 0.05. Se encontró una media de puntuación de riesgo coronario de 18.22 ± 3.49 puntos (12- 29 puntos), que se clasifica como riesgo medio. En cuanto a grupos de edad el riesgo coronario reportado fue de 16.58 ± 3.11 puntos para los individuos del grupo 18- 20 años, 18.21 ± 3.08 puntos para 21- 30 años, 20.58 ± 3.89 puntos para 31- 40 años, y 21.00 ± 4.53 para los mayores de 40 años. Para cada factor de riesgo, la prevalencia observada, en orden descendente, fue: sobrepeso (44.78%), inactividad física (38.31%), hipercolesterolemia (24.38%), tabaquismo (17.41%), herencia (12.94%) e hipertensión (8.46%). Los factores de riesgo coronario de mayor prevalencia en los jugadores recreacionales de fútbol fueron la inactividad física, el sobrepeso y la hipercolesterolemia, con una clasificación de riesgo medio y con aumento del riesgo con la edad, especialmente después de 31 años.To determine the prevalence of coronary risk factors in recreational soccer players and compare the coronary risk according to age. Methods: 201 men who practiced soccer recreationally eere evaluated, with a mean age of 25.26 ± 5.96 years. All individuals answered the questionnaire RISKO, which is a questionnaire containing eight risk factors. The coronary risk is represented by the sum of the scores obtained in the eight risk factors. Statistical analysis consisted of descriptive exploration and one way ANOVA with post hoc Tukey, to compare coronary risk between age groups. We adopted a significance level of p < 0.05. The mean coronary risk was 18.22 ± 3.49 points (12- 29 points), classified as medium risk. Regarding age groups the mean coronary risk obtained was: 16.58 ± 3.11 points for individuals between 18 and 20 years; 18.21 ± 3.08 points for those between 21 and 30 years, 20.58 ± 3.89 points for subjects between 31 and 40 years, and 21.00 ± 4.53 for those aged over 40 years. For each risk factor, the prevalence observed in descending order, was: overweight (44.78%), physical inactivity (38.31%), hypercholesterolemia (24.38%), smoking (17.41%), inheritance (12.94%) and hypertension (8.46%). The coronary risk factors more prevalent in recreational soccer players were overweight, physical inactivity and hypercholesterolemia, showing increased with increasing age, especially after 31 years

Trastuzumab-Induced Myocardiotoxicity Mimicking Acute Coronary Syndrome

Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6–4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion

Integridade estrutural de compósitos laminados em fibra de carbono sujeitos a diferentes taxas de desgaste e absorção de água : protótipo de máquina de testes

Trabalho final de mestrado para obtenção do grau de Mestre em Engenharia MecânicaDesde sempre no panorama do ciclismo de alta competição se fizeram todos os esforços para melhorar os resultados dos atletas. Grande parte destes trabalhos está no desenvolvimento das bicicletas e seus componentes. A empresa Morphis Composites que está em fase de desenvolvimento de carretos de desviador em fibra de carbono. Estando estes componentes em material compósito laminado expostos à atmosfera, poderá estar em causa a sua integridade estrutural pois sabe-se que irão absorver água por difusão e se vão desgastar de forma diferente de carretos de outros materiais. Tudo isto poderá levar ao aumento do seu atrito na transmissão, sendo que é necessária a criação de meios para a avaliação desta temática. No presente trabalho faz-se o projecto e construção de um protótipo para medição de atrito em transmissões de bicicleta. Inclui-se uma breve pesquisa bibliográfica sobre correntes de rolos industriais e de ciclismo, o seu funcionamento e mecanismos de atrito. Além disto fez-se também uma breve pesquisa sobre os efeitos da absorção de água na fibra de carbono. Para o dimensionamento do sistema de medição procuraram-se resultados de trabalhos similares de forma a aferir as grandezas a medir e a sensibilidade necessária. O protótipo deve medir a potência conduzida à transmissão para esta rodar em vazio a uma velocidade constante que foi fixada neste caso em 60 rpm, sendo que quanto mais baixa a potencia medida menor o atrito da transmissão. O sensor usado é uma roseta colada a +45 e -45 graus no veio que fornece movimento ao sistema. O sinal é retirado do veio em rotação através de um sistema de anéis deslizantes em bronze onde se usaram escovas de grafite e de filamentos de cobre. Após a construção do protótipo fez-se a calibração estática dos sistemas de medição com bons resultados de sensibilidade e repetibilidade. Estes resultados empíricos também foram comparados com os resultados teóricos não tendo havido discrepâncias relevantes, provando a qualidade das medições de binário obtidas pelos extensómetros. No entanto, devido ao ruído introduzido no sinal pelas escovas em movimento, não foi possível obter resultados de qualidade nos ensaios dinâmicos para a potência e atrito na transmissão em rotação com o presente protótipo. No final apresentam-se sugestões para melhoria em trabalhos futuros.Ever since the beginning of high competition in cycling, that every erffort has been made to improve the results of the athletes. Much of this work is in the development of bicycles and their components. The company Morphis Composites is in the development stage of carbon fiber rear derailleur sprockets. These components made of laminated composite material are exposed to the atmosphere, thus their structural integrity may be affected because it is known that they will absorb water by diffusion and will wear differently from sprockets made of other materials, such as metals. All this can lead to the increase of its friction in the transmission, and it is necessary to create means for the evaluation of this situation. In the present work, the design and construction of a prototype for measuring friction in bicycle transmissions is done. A brief literature review on industrial roller and cycling chains, their operation and friction mechanisms is included. In addition, a brief research was also made on the effects of water absorption on carbon fiber. For the sizing of the measurement system, results of similar work were sought in order to understand the quantities to be measured and the required sensitivity. The prototype shall measure the power delivered to the transmission to idle at a constant speed which has been set at 60 rpm in this case, the lower the measured power the lower the transmission friction. The sensor used is a rosette glued to +45 and -45 degrees in a section of the main shaft before the main sprocket. The signal is drawn from the rotating shaft through a bronze slip ring system where graphite brushes and copper filaments were used. Upon prototype building the static calibration of the measurement systems was made with good results of sensitivity and repeatability. These empirical results were also compared with what would theoretically be expected and there were no relevant discrepancies, proving the quality of the torque measurements obtained by the extensometers. However, due to the noise introduced into the signal by the moving brushes, it was not possible to obtain quality results in the dynamic tests for power and friction in the rotational transmission with the present prototype. At the end, suggestions are presented for improvement in future work.N/

Cytotoxic Effects Of Zoledronic Acid On Human Epithelial Cells And Gingival Fibroblasts

Bisphosphonate-induced osteonecrosis has been related to the cytotoxicity of these drugs on oral mucosa cells. A previous study showed that 5 μM of zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is the highest concentration of this drug found in the oral cavity of patients under treatment. Therefore, in order to simulate an osteonecrosis clinical condition, the aim of this study was to evaluate the highest concentration of ZA applied on human epithelial cells (HaCaT) and gingival fibroblasts. For this purpose, cells (3x104 cells/cm2) were seeded in wells for 48 h using complete culture medium (cDMEM). After 48 h incubation, the cDMEM was replaced by fresh serum-free culture medium (DMEM-FBS) in which the cells were maintained for additional 24 h. Then, 5 μM ZA were added to the DMEM-FBS and the cells incubated in contact with the drug for 48 h. After this period, the number of viable cells (trypan blue), cell viability (MTT assay), total protein (TP) production and cell morphology (SEM analysis) were assessed. Data were analyzed statistically by Mann-Whitney, ANOVA and Tukey's test (α=0.05). ZA caused a significant reduction in the number of viable cells and decreased the metabolic activity of both cell lines. However, decrease of TP production occurred only in the epithelial cell cultures. Morphological alterations were observed in both cell types treated with ZA. In conclusion, ZA (5 μM) was cytotoxic to human epithelial cells and gingival fibroblast cultures, which could be associated, clinically, with the development of bisphosphonateinduced osteonecrosis.246551558Civitelli, R., Napoli, N., Armamento-Villareal, R., Use of intravenous bisphosphonates in osteoporosis (2007) Curr Osteoporos Rep, 5, pp. 8-13Cohen, S.B., An update on bisphosphonates (2004) Curr Rheumatol Rep, 6, pp. 59-65Rogers, M.J., Watts, D.J., Russel, R.G., Overview of bisphosphonates (1997) Cancer, 80, pp. 1652-1660Rogers, M.J., Gordon, S., Benford, H.L., Coxon, F.P., Luckman, S.P., Monkkonen, J., Cellular and molecular mechanisms of action of bisphosphonates (2000) Cancer Supl, 88, pp. 2961-2978Lawson, M.A., Xia, Z., Barnett, B.L., Triffitt, J.T., Phipps, R.J., Dunford, J.E., Differences between bisphosphonates in binding affinities for hydroxyapatite (2010) J Biomed Mater Res Part B: Appl Biomater, 92, pp. 149-155Allen, M.R., Burr, D.B., The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: So many hypotheses, so few data (2009) J Oral Maxillofac Surg, 67, pp. 61-70Otto, S., Pautke, C., Opelz, C., Wesphal, I., Drosse, I., Swager, J., Osteonecrosis of the jaw: Effects of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism (2010) J Oral Maxillofac Surg, 68, pp. 2837-2845Reid, I.R., Booland, M.J., Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? (2007) Bone, 41, pp. 318-320Scheper, M.A., Badros, A., Chausparat, R., Cullen, K.J., Meiller, T.F., Effect of zoledronic acid on oral fibroblasts and epithelial cells: A potential mechanism of bisphosphonate-associated osteonecrosis (2009) Br J Haematol, 144, pp. 667-676Scheper, M.A., Badros, A., Salama, A.R., Wartburton, G., Cullen, K.J., Weikel, D.S., A novel bioassay model to determine clinically significant bisphosphonate levels (2009) Support Care Cancer, 17, pp. 1553-1557Ruggiero, S.L., Mehrotra, B., Rosenberg, T.J., Engroff, S.L., Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases (2004) J Oral Maxillofac Surg, 62, pp. 527-534Walter, C., Klein, M.O., Pabst, A., Al-Nawas, B., Duscher, H., Ziebart, T., Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells (2010) Clin Oral Investig, 14, pp. 35-41Kumar, S.K.S., Gorur, A., Schaauddin, C., Shuler, C.F., Costerton, J.W., Sedghizadeh, P.P., The role of microbial biofilms in osteonecrosis of the jaw associated with bisphosphonate therapy (2010) Curr Osteoporos Rep, 8, pp. 40-48Aas, J.A., Paster, B.J., Stokes, L.N., Olsen, I., Dewhirst, F.E., Defining the normal bacterial flora of the oral cavity (2005) J Clin Microbiol, 43, pp. 5721-5732Basso, F.G., Pansani, T.N., Turrioni, A.P.S., Bagnato, V.S., Hebling, J., de Souza Costa, C.A., In vitro wound healing improvement by low-level laser therapy application in cultured gingival fibroblasts (2012) Int J Dent, , [Epub ahead of print. DOI: 10.1155/2012/719452]Wiegand, C., Hipler, U., Methods for the measurement of cell and tissue compatibility including tissue regeneration process (2008) GMS Krankenhhyg Interdiszip, 3, pp. 1863-5245Basso, F.G., Oliveira, C.F., Kurachi, C., Hebling, J., de Souza Costa, C.A., Biostimulatory effect of low-level laser therapy on keratinocytes in vitro (2013) Lasers Med Sci, 28, pp. 367-374De Souza Costa, C.A., Duarte, P.T., de Souza, P.P., Giro, E.M., Hebling, J., Cytotoxic effects and pulpal response caused by a mineral trioxide aggregate formulation and calcium hydroxide (2008) Am J Dent, 21, pp. 255-261Oliveira, C.F., Basso, F.G., Lins, E.C.C., Kurachi, C., Hebling, J., Bagnato, V.S., Increased viability of odontoblast-like cells subjected to low-level laser irradiation (2010) Laser Phys, 20, pp. 1659-1666Read, S.M., Northcote, D.H., Minimization of variation in the response to different proteins of the Coomassie blue G dye-binding assay for protein (1981) Anal Biochem, 116, pp. 53-64Oliveira, C.F., Basso, F.G., Lins, E.C., Kurachi, C., Hebling, J., Bagnato, V.S., In vitro effect of low-level laser on odontoblast-like cells (2011) Laser Phys Lett, 8, pp. 155-163Simon, M.J.K., Niehoff, P., Kimming, B., Wiltfang, J., Açil, Y., Expression profile and synthesis of different collagen types I, II III and V of human gingival fibroblasts, osteoblasts, ans SaOs-2 cells after bisphosphonate treatment (2010) Clin Oral Investig, 14, pp. 51-58Migliorati, C.A., Siegel, M.A., Elting, L.S., Bisphosphonate-associated osteonecrosis: A long-term complication of bisphosphonate treatment (2006) Lancet Oncol, 7, pp. 508-514Werner, S., Krieg, T., Smola, H., Keratinocyte-fibroblast interactions in wound healing (2007) J Investigative Dermatol, 127, pp. 998-1008Ravosa, M.J., Ning, J., Liu, Y., Stack, M.S., Bisphosphonate effects on the behavior of oral epithelial cells and oral fibroblasts (2011) Arch Oral Biol, 56, pp. 491-49

Macroecological and biogeographical patterns of limb reduction in the world's skinks

First published: 08 December 2022Aim: Limb reduction is a dramatic evolutionary transition, yet whether it is achieved in similar trajectories across clades, and its environmental drivers, remain unclear. We investigate the macroevolutionary and biogeographical patterns of limb reduction in skinks, where limb reduction occurred more often than in any other tetrapod clade, and test their associations with substrate categories using a global database. We test for habitat associations of body shapes in a group of Australian skinks using quantitative habitat data. Location: Global (Scincidae), Australia (Sphenomorphinae). Taxon: Skinks, Australian Sphenomorphinae. Materials and Methods: We use morphological data to explore the patterns of limb reduction in the world's skinks, investigating how body proportions differ across skink clades and subfamilies. We examine the relationships between body shape and substrate (coarsely classified). Further, we investigate the relationships between body shape and high-resolution soil and climate properties extracted from each species' distribution for Australian sphenomorphines. Results: Relationships between limb lengths and trunk elongation show idiosyncratic patterns across skink clades. Presacral vertebrae numbers positively correlate with trunk elongation in all taxa, except Glaphyromorphus. Skinks from sandy habitats show greater disparity between forelimb and hindlimb lengths than all other substrate categories. In sphenomorphines, shorter limbs and elongated trunks correlate with colder, more humid microhabitats and richer soils; high limb disparity correlates with hot, arid microhabitats and sandy, poor substrates. Main Conclusions: The evolutionary trajectories of limb reduction in skinks are cladespecific and sometimes unique. Selection for specific limb proportions and body sizes in limb-reduced forms changes across substrates. On poor, sandy substrates of arid environments, body shapes with longer hindlimbs may be more efficient for locomotion in a granular fluid (i.e. sand) and exploit the air–substrate interface than complete limblessness. On richer, more humid substrates, such morphology is rare, indicating that navigating cluttered substrates selects for more equal and shorter limb lengths.Marco Camaiti, Alistair R. Evans, Christy A. Hipsley, Mark N. Hutchinson, Shai Meiri, Rodolfo de Oliveira Anderson, Alex Slavenko, David G. Chappl

Clinical presentation, histological findings, and prognosis in female dogs with mixed mammary neoplasms

ABSTRACT The aim of this study was to describe the clinical and morphological characteristics of mixed mammary neoplasms and verify what characteristics affect the prognosis of female dogs with carcinomas in mixed tumors and carcinosarcomas. This was a retrospective study of 67 female dogs that underwent mastectomies and were diagnosed with benign mixed tumors (n=13), carcinomas in mixed tumors (n=44) and carcinosarcomas (n=10). Data regarding the clinical and histological aspects of the neoplasms were collected and the relation with specific survival times, and hazard ratios (HR) in 24 months was calculated. In univariate analysis, the diagnosis of carcinosarcoma (HR 8.26, p=0.006), carcinomatous areas with micropapillary or solid patterns (HR 17.49; p=0. 001) and lymph node metastasis (HR 7.07;p=0.020) were associated with specific survival. In multivariable analysis, only micropapillary or solid pattern (HR=16.34; p=0.007) remained independent factor associated with lower specific survival. Micropapillary or solid carcinomatous patterns were associated with shorter specific survival time (p=0.002) among animals with carcinomas in mixed tumors. Among the carcinosarcomas, lymph node metastasis (p=0.010) was associated with a shorter specific survival time. In conclusion, carcinomas in mixed tumors and carcinosarcomas vary in prognosis depending on the carcinomatous proliferation patterns and spread of the disease

Lower bounds for measurable chromatic numbers

The Lovasz theta function provides a lower bound for the chromatic number of finite graphs based on the solution of a semidefinite program. In this paper we generalize it so that it gives a lower bound for the measurable chromatic number of distance graphs on compact metric spaces. In particular we consider distance graphs on the unit sphere. There we transform the original infinite semidefinite program into an infinite linear program which then turns out to be an extremal question about Jacobi polynomials which we solve explicitly in the limit. As an application we derive new lower bounds for the measurable chromatic number of the Euclidean space in dimensions 10,..., 24, and we give a new proof that it grows exponentially with the dimension.Comment: 18 pages, (v3) Section 8 revised and some corrections, to appear in Geometric and Functional Analysi