Investigation of the role of protein kinase C (PKC) in cytostasis induced by tumour promoting phorbol esters and related compounds

Protein kinase C (PKC) is considered to be the major receptor for tumour promoting phorbol esters such as 12-0- tetradecanoylphorbol-13-acetate (TPA). These agents evoke a plethora of biological effects on cells in culture. The growth of A549 human lung carcinoma cells maintained in medium fortified with 10% foetal calf serum (FCS) is arrested for 6 days by TPA and other biologically active phorbol esters. In the work described in this thesis, the hypothesis was tested that modulation of PKC activity is closely related to events pivotal for cytostasis to occur. The effect of several phorbol esters, of newly synthesized analogues of diacylglycerols (DAG) and of bryostatins (bryos) on cell growth and ability to modulate activity of PKC has been investigated.Determination of the subcellular distribution of PKC following treatment of cells with TPA and partial enzyme purification by non-denaturing poly-acrylamide gel electrophoresis revealed translocation of enzyme activity from cytosoUc to paniculate fraction. Chronic exposure of cells to TPA resulted in a time and concentration dependent degradation of enzyme activity. Synthetic DAG and DAG analogues, unable to arrest the growth of cells at non-toxic concentrations, were neither able to affect subcellular PKC distribution nor compete effectively for phorbol ester binding sites at physiologically relevant concentrations. Bryos 1,2,4 and 5, natural products, possessing antineoplastic activity in mice, elicited transient arrest of A549 cell growth in vitro. They successfully competed for phorbol ester receptors in A549 cells with exquisite affinity and induced a shift in sub-cellular PKC distribution, though not to the same extent as PTA. Enzyme down-regulation resulted from prolonged exposure of cells to nanomolar concentrations of bryos. In vivo studies demonstrated that neither PDBu nor bryo 1 was able to inhibit A549 xenograft growth in athymic mice. The growth of A549 cell populations cultured under conditions of serum-deprivation was inhibited only transiently by biologically active phorbol esters. Fortification of serum-free medium with EGF or fetuin was able to partially restore sensitivity to maintained growth arrest by PTA. PKC translocation to the paniculate cellular fraction and subsequent enzyme down-regulation, induced by TPA, occurred in a manner similar to that observed in serum-supplemented cells. However, total PKC activity and cytosolic phorbol ester binding potential were greatly reduced in the serum-deprived cell population. Western blot analysis using monospecific monoclonal antibodies revealed the presence of PKC-a in both A549 cell populations, with significantly reduced protein levels in serum- deprived cells. PKC-/9 was not detected in either cell population.

HIV, cardiovascular diseases, and chronic arsenic exposure co-exist in a positive synergy

Recent epidemiological evidences indicate that arsenic exposure increases risk of atherosclerosis, cardio vascular diseases (CVD) such as hypertension, atherosclerosis, coronary artery disease (CAD) and microangiopathies in addition to the serious global health concern related to its carcinogenic effects. In experiments on animals, acute and chronic exposure to arsenic directly correlates with cardiac tachyarrhythmia, and atherogenesis in a concentration and duration dependent manner. Moreover, the other effects of long-term arsenic exposure include induction of non-insulin dependent diabetes by mechanisms yet to be understood. On the other hand, there are controversial issues, gaps in knowledge, and future research priorities in accelerated incidences of CVD and mortalities in patients with HIV who are under long-termanti-retroviral therapy (ART). Although, both HIV infection itself and various components of ART initiate significant pathological alterations in the myocardium and the vasculature, simultaneous environmental exposure to arsenic which is more convincingly being recognized as a facilitator of HIV viral cycling in the infected immune cells, may contribute an additional layer of adversity in these patients. A high degree of suspicion and early screening may allow appropriate interventional guidelines to improve the quality of lives of those affected. In this mini-review which have been fortified with our own preliminary data, we will discuss some of the key current understating of chronic arsenic exposure, and its possible impact on the accelerated HIV/ART induced CVD. The review will conclude with notes on recent developments in mathematical modeling in this field that probabilistically forecast incidence prevalence as functions of aging and life style parameters, most of which vary with time themselves; this interdisciplinary approach provides a complementary kernel to conventional biology.

Financial crisis and the change in the practice of applying common charge costs

The global financial crisis has not left the members of the EU untouched. Financial results have significantly dropped, businesses were folded in great numbers, the rate of employment decreased, social tension got fortified, and so did the national deficits in the budget in the majority of the countries. The decisive members of the community reacted fairly quickly to the challenges of the global economic crisis, and among the steps taken there were simultaneously ones to boost the economy and others to lower the expenses of the expenditure. The author examines what role was given to the steps in taxation policy as indirect regulating tools, and that how the decisions brought touch upon the previously issued harmonization strategy.

Rio and the Reds: The Comando Vermelho, Organized Crime and Brazil’s Economic Ascent [Student’s Paper Series]

Brazil’s growing status as a potential world power cannot obscure the characteristics of its other reality: that of a country with vast inequalities and high crime rates. The Comando Vermelho, the most prominent organized crime syndicate in Rio de Janeiro, besieges the beauty and charm that attracts tourists to this city. The CV arose not only as a product of the political dictatorship of the seventies, but also of the disenfranchised urban poor crammed into Rio’s favela slums. Today, the CV presents a powerful challenge to the State’s control of parts of Rio territory. As Brazil’s soft power projection grows, it is seriously challenged by its capacity to eliminate organized crime. Economic growth is not sufficient to destroy a deeply embedded organization like the CV. In fact, Brazil’s success may yet further retrench the CV’s activities. Culpability for organized crime cannot be merely limited to the gangs, but must also be shared among the willing consumers, among whom can be found educated and elite members of society, as well as the impoverished and desperate. The Brazilian government needs a top-down response addressing the schism between rich and poor. However, Brazil’s citizens must also take responsibility and forge a bottom-up response to the drug- and corruption-riddled elements of its most respected members of society. Brazil must target reform across public health, housing, education and above all, law enforcement. Without such changes, Brazil will remain a two-track democracy. Rio’s wealthy will still be able to revel in the city’s beauty albeit from behind armored cars and fortified mansions, while the city’s poor will yield – either as victims or perpetrators – to the desperate measures of organized crime.

Un -equal opportunity: Sex and school among first and second generation Mexican immigrant adolescent girls

The purpose of this dissertation was to determine the interactions of sexuality and education among low socioeconomic status first and second generation Mexican immigrant adolescent girls. Much of the existing research differentiates between immigrant generations with little examination of the differences within a particular immigrant generation. This study utilized qualitative methods to examine how various social institutions intersected to influence the young women's decisions about education and sexuality. The methodology included more than three years of participant observation in a South Florida high school and surrounding community; structured and unstructured interviews with twenty young women, their family members, school personnel, and community activists; and surveys conducted with the young women and their parent or guardian. ^ Moving beyond the limits of essentialist immigration theories, this project revealed within group (i.e. immigrant generation) complexities as well as between group similarities. The data included in this dissertation delineate how relationships of power and control permeated the lives of first and second generation Mexican immigrant adolescent girls. The lens of this dissertation is focused on the salient issues of sexuality and education: two dominant forces in many adolescent lives. ^ I found the young women represented a variety of positions on the academic orientation and sexuality continuums and engaged in activities that both reinforced and countered their stated positions on each of these issues. Specifically, first and second generation immigrants are often viewed as maintaining opposing viewpoints about both education and female sexuality however, for these young women the within group variation was larger than the between group variation. While all the young women in this study expressed a belief in the value of education, they engaged in activities that both fortified and contradicted that expressed position. Additionally, although acculturation can lead to increased sexual activity and decreased engagement with education, the first generation immigrant young women in this study became pregnant and/or withdrew from school in equal proportions to their second generation counterparts. In summary, structural forces combined, often inadvertently, and contributed to these young women's spiraling negative academic orientation and/or rational choice of motherhood. Finally, the findings are linked to policy implications. ^

The Perceptions, Attitudes and Practices of Registered Dietitians Regarding Functional Foods

The term “functional food” (FF) has a variety of definitions resulting in term ambiguity. It is unclear Registered Dietitians’ (RDs) understanding and practices about FF. A descriptive, cross-sectional study investigated RDs’ perceptions, attitudes and practices regarding FF. A national random sample (n=1800) of RDs was mailed a FF questionnaire, 385 (22%) responded. Given five definitions from food-nutrition authorities, the majority of RDs did not agree on a definition, although three-fourths (n=292, 75.8%) perceived fortified foods as FF. Registered Dietitians agreed FF could improve health (n=266, 69.1%), prevent disease (n=282, 73.2%) and treat clientele (n=246, 63.9%), however were neutral (41.6%) or disagreed (37.7%) FF were herbs, or equivalent to medicine (32.7%, 49.2% respectively). Most RDs (n=290, 75.9%) ate FF; fewer (n=231, 61.4%) professionally recommended them. Nearly all (n=353) indicated interest in learning about FF. Registered Dietitians revealed inconsistencies between their perceptions, attitudes and practices regarding FF. Professional education is needed to resolve discrepancies regarding FF.

A ADESÃO PENTECOSTAL DE BANDIDOS E EX-BANDIDOS – UM ESTUDO SOBRE RELIGIÃO E PERIFERIA NA FAVELA DO JARDIM SÃO JORGE EM CIDADE ADEMAR - SP

A dissertação preocupou-se em analisar as relações de bandidos e ex-bandidos com o pentecostalismo na Assembleia de Deus Fortificada em Cristo (ADFEC), situada na favela Jardim São Jorge, periferia da Cidade Ademar, região Sul da capital de São Paulo. Interessou-nos compreender as interações desses agentes e de qual maneira a igreja desempenhou seu trabalho em um espaço pentecostal. A pesquisa, teve como objetivo fundamental, examinar as aproximações da criminalidade e o pentecostalismo indicando suas rupturas e características peculiares. O trabalho de campo se dedicou em coletar dados que comprovassem atuação da ADFEC juntos aos agentes do crime, e em que medida a filiação religiosa dos agentes ganhava importância. Por fim, buscamos refletir sobre a adesão de bandidos e ex-bandidos ao pentecostalismo e a influência dessa adesão no cotidiano da comunidade.

Iron status in early life and associations with developmental outcomes

Infants and young children are at particular risk of iron deficiency and its associated consequences for growth and development. The main objectives of this thesis were to quantify iron intakes, status and determinants of status in two year olds; explore determinants of neonatal iron stores; investigate associations between iron status at birth and two years with neurodevelopmental outcomes at two years and explore the influence of growth on iron status in early childhood, using data from the Cork BASELINE (Babies after SCOPE: Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n=2137). Participants were followed prospectively with interviewer-led questionnaires and clinical assessments at day 2 and at 2, 6, 12 and 24 months. At two years, there was a low prevalence of iron deficiency and iron deficiency anaemia in this cohort, representing the largest study of iron status in toddlers in Europe, to date. The increased consumption of iron-fortified products and compliance with recommendations to limit unmodified cows’ milk intakes in toddlers has contributed to the observed improvements in status. Low serum ferritin concentrations at birth, which reflect neonatal iron stores, were shown to track through to two years of age; delivery by Caesarean section, being born small-for-gestational age and maternal obesity and smoking in pregnancy were all associated with significantly lower neonatal iron stores. Despite a low prevalence of iron deficiency in this cohort, both a mean corpuscular volume <74fl and ferritin concentrations <20μg/l were associated with lower neurodevelopmental outcomes at two years. An inverse association between growth in the second year of life and iron status at two years was also observed. This thesis has presented data from one of the largest, extensively-characterised cohorts of young children, to date, to explore iron and its associations with growth and development.

Vitamin D and Health

SACN reviewed the evidence on vitamin D and health to see if UK dietary recommendations, set in 1991, were still appropriate. In addition to the main report, you can read the SACN press release. In a change to previous advice, SACN is now recommending: a reference nutrient intake (RNI) of 10 micrograms of vitamin D per day, throughout the year, for everyone in the general population aged 4 years and older an RNI of 10 micrograms of vitamin D per day for pregnant and lactating women and population groups at increased risk of vitamin D deficiency a ‘safe intake’ of 8.5 to 10 micrograms per day for all infants from birth to 1 year of age a ‘safe intake’ of 10 micrograms per day for children aged 1 to 4 years The RNI and safe intakes were developed to ensure that the majority of the UK population has enough vitamin D to protect musculoskeletal health, all year round. SACN did not take account of sunlight exposure in making recommendations because of the number and complexity of factors that affect skin synthesis of vitamin D. The RNI and safe intakes refer to intake from all dietary sources: natural food sources fortified foods (including infant formula milk) supplements They also refer to average intakes over a period of time, such as a week, and take account of day-to-day variations in intake.

Impacte ambiental da viticultura do Douro na qualidade dos solos, sedimentos e águas

A atividade vitícola praticada na região do Douro é uma das mais importantes atividades agrícolas do país, não só devido a fatores socioculturais, como também pelo seu valor económico. A Região Demarcada do Douro (RDD) é uma das regiões vitícolas mais antiga do mundo, onde é produzido um dos vinhos generosos mais famosos do mundo, o Vinho do Porto. Contudo, no cultivo intensivo da vinha, o uso recorrente a pesticidas para o controlo de pragas das vinhas pode ter repercussões a nível da qualidade dos solos e dos cursos de água na envolvente às vinhas. O presente estudo foi desenvolvido numa área-piloto da sub-região Baixo Corgo da RDD, com o intuito de averiguar os possíveis efeitos e estimar os prováveis riscos ambientais promovidos pela viticultura. Foram selecionadas três vinhas, com idades de plantação distintas, onde foram recolhidas amostras de solos à superfície, tendo-se ainda feito uma recolha de amostras de água, sedimentos e águas intersticiais dos rios e da barragem na envolvente da área de estudo. Diferentes parâmetros químicos e físico-químicos foram analisados para uma avaliação global da área e prováveis fontes dos elementos. Especial destaque foi dado ao Cu, C, P, N, NO3 e S quer pelos teores anómalos e elevada variação espacial, quer pela sua importância como traçadores das atividades vitícolas e alguns como potenciais contaminantes. O Cu é o elemento potencialmente contaminante com mais destaque, visto que os seus teores são consideravelmente elevados nos solos e, a par, o P e N tendem a apresentar teores mais elevados na vinha mais velha, o que pode indicar efeitos de acumulação. Já os nitratos são mais elevados na vinha mais nova, visto que os processos de acumulação são mais difíceis neste caso devido à sua alta solubilidade e mobilidade. Apesar da elevada aplicação de S nas vinhas, os teores nestes solos são mais baixos do que nos solos sem atividades vitícolas, o que pode dever-se à sua baixa temperatura de sublimação e migração para níveis mais profundos dos solos. As baixas concentrações determinadas nos sedimentos e águas permitem concluir que as práticas vitícolas não parecem estar a interferir na qualidade dos mesmos. Contudo, novas campanhas de amostragem, abrangendo períodos sazonais distintos e próximos de épocas de aplicação de fertilizantes e pesticidas, deverão ser realizadas para validação temporal destes resultados.

Encapsulation of ascorbic acid promotes the reduction of Maillard reaction products in UHT milk

The presence of amino groups and carbonyls renders fortified milk with ascorbic acid particularly susceptible to the reduction of available lysine and to the formation of Maillard reaction products (MRPs), as Nε-(Carboxyethyl)-L-lysine (CEL), Nε-(Carboxymethyl)-L-lysine (CML), Amadori products (APs) and off-flavors. A novel approach was proposed to control the Maillard reaction (MR) in fortified milk: ascorbic acid was encapsulated in a lipid coating and the effects were tested after a lab scale UHT treatment. Encapsulation promoted a delayed release of ascorbic acid and a reduction in the formation of MRPs. Total lysine increased up to 45% in milk with encapsulated ascorbic acid, while reductions in CML, CEL and furosine ranged from 10% to 53% compared with control samples. The effects were also investigated towards the formation of amide-AGEs (advanced glycation end products) by high resolution mass spectrometry (HRMS) revealing that several mechanisms coincide with the MR in the presence of ascorbic acid (AA).

got your dairy today? : 10 tips to help you eat and drink more fat-free or low-fat dairy foods

The Dairy Group includes milk, yogurt, cheese, and fortified soymilk. They provide calcium, vitamin D, potassium, protein, and other nutrients needed for good health throughout life. Choices should be lowfat or fat-free—to cut calories and saturated fat. How much is needed? Older children, teens, and adults need 3 cups* a day, while children 4 to 8 years old need 2½ cups, and children 2 to 3 years old need 2 cups.

Desenvolvimento de método para determinação de resíduos de sedativos e B-bloqueadores em rim por LC-MS/MS

O desenvolvimento de métodos adequados que permitam o monitoramento de resíduos e contaminantes em alimentos é de suma importância pois é a única forma de garantir a segurança dos alimentos evitando danos à saúde do consumidor. Para isso, fazse necessário que estes métodos sejam rápidos, fáceis e de baixo custo, capazes de detectar a presença de resíduos em concentrações baixas e em diferentes matrizes. Este trabalho consistiu no desenvolvimento de método para determinação de 5 sedativos e 14 β-bloqueadores em amostras de rim suíno e posterior análise por Cromatografia Líquida Acoplada à Espectrometria de Massas em Série (LC-MS/MS). O procedimento de extração que melhor se adequou para análise destes compostos consistiu na pesagem de 2 g de amostra e adição de 10 mL de acetonitrila seguida de homogeneização com auxílio de Ultra-Turrax e mesa agitadora. Após extração, as amostras foram submetidas a duas técnicas de clean-up, sendo elas, congelamento do extrato à baixa temperatura e extração em fase sólida dispersiva (d-SPE) utilizando como sorvente Celite® 545. Uma etapa de concentração foi realizada com auxílio de concentrador de amostras sob fluxo de N2 e temperatura controlada. As amostras secas foram retomadas com metanol e analisadas utilizando sistema LC-MS/MS com Ionização por Eletrospray (ESI), operando no modo MRM positivo, coluna Poroshell 120 EC-C18 (3,0 x 50 mm, 2,7 μm) para separação dos analitos, e gradiente de fase móvel composta por (A) solução aquosa acidificada com 0,1% de ácido fórmico (v/v) e (B) metanol 0,1% ácido fórmico (v/v). Os parâmetros de validação avaliados foram linearidade, seletividade, efeito matriz, precisão, veracidade, recuperação, limite de decisão, capacidade de detecção, incerteza da medição, robustez, limite de detecção e de quantificação. Além disso foram observados os critérios de desempenho aplicáveis à detecção por espectrometria de massas e estabilidade dos compostos. A recuperação foi avaliada em 10 μg kg-1 e a veracidade em 5, 10 e 15 μg kg-1 apresentando resultados satisfatórios entre 70 - 85% e 90 - 101%, respectivamente. O limite de quantificação determinado foi de 2,5 μg kg-1 , exceto para carazolol que foi de 1,25 μg kg- 1 . O estudo de linearidade foi realizado entre 0 e 20 μg kg-1 apresentando coeficientes de determinação superiores a 0,98. Estes procedimentos foram realizados através de análise de matriz branca fortificada. Além disso, o presente método foi utilizado para analisar carazolol, azaperone e azaperol em amostras de ensaio colaborativo de rim suíno, apresentando resultados muito próximos aos reais. Portanto, é possível concluir que o método desenvolvido é adequado para análise de sedativos e β-bloqueadores através de extração dos compostos e limpeza do extrato eficientes utilizando procedimentos rápidos, fáceis e de baixo custo, garantindo resultados seguros e confiáveis.

Desenvolvimento de sistema automatizado para o monitoramento da degradação de resíduos de brometo de etídio

Tese (doutorado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Química, 2015.

Um olhar sobre o castelo de Noudar: do castelo medieval à ruína: Proposta de valorização do lugar

O Castelo de Noudar está implantado num íngreme promontório da herdade da Coitadinha, a Noroeste de Barrancos, integrando o atual Parque da Natureza de Noudar. Construído a partir de 1303, foi alvo de diversas transformações ao longo do tempo, para responder às exigências militares de cada época, e chega aos nossos dias num avançado estado de decadência física. A investigação desenvolvida assenta, em grande parte, no desenho: de Noudar a uma escala territorial, como elemento que participa numa rede fortificada complexa; da evolução morfológica e funcional, que nos permite ter noção das várias configurações do castelo ao longo dos séculos; num desenho propositivo que desenvolve uma estratégia para valorização do lugar e do seu património material e imaterial. Hoje é fundamental compreender como as valências do Parque e da fortaleza se podem cruzar? Este trabalho pretende refletir sobre possibilidades de valorização para contrariar a degradação em que a fortaleza se encontra; ABSTRACT: The Noudar Castle is located in a steep promontory in the herdade da Coitadinha, Northeast from Barrancos, part of the Natural Park of Noudar. Its construction began in 1303, and underwent several transformations throughout its existence, adapting to the military advancements thru out the ages. Today, it shows an advanced state of decay. The investigation is focused on the design of Noudar on a territorial scale, taking part in a complex network of fortified systems; its functional and morphological evolution, which allows us to comprehend the configurations of the castle throughout the centuries; and on a proposed design that develops a strategy to enhance and bring value to this place and its material and non-material heritage. Today it's crucial to comprehend how can the values of the Park and fortress intertwine. This thesis reflects on the possibilities of valuing this site, counter acting the decay which has fallen upon it.