Synthesis of potentially bioactive PABA-related N-(aminoalkyl)lactamic amino acids and esters via selective SNAr reactions

Potentially bioactive N-(aminoalkyl)lactamic amino acids and esters were synthesized in satisfactory to good yields by SNAr reactions of aromatic acids with N-(3-aminopropyl)lactams followed by esterification with tertiary amino alcohols. The addition-elimination SNAr mechanism was confirmed by NMR and MS measurements.

Síntese e caracterização de amino ácidos e ésteres n-(aminoalquil)-lactâmicos derivados do paba com potencial atividade biológica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Síntese de N-Alquilsulfonamidas análogas do PABA com potencial atividade antagonista de canais iônicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Substrate-dependent regulation of human arylamine N-acetyltransferase-1 in cultured cells

Arylamine N-acetyltransferase-1 (NAT1) is a polymorphically expressed enzyme that is widely distributed throughout the body. In the present study, we provide evidence for substrate-dependent regulation of this enzyme. Human peripheral blood mononuclear cells cultured in medium supplemented with p-aminobenzoic acid (PABA; 6 mu M) for 24 h showed a significant decrease (50-80%) in NAT1 activity. The loss of activity was concentration-dependent (EC50 similar to 2 mu M) and selective because PABA had no effect on the activity of constitutively expressed lactate dehydrogenase or aspartate aminotransferase. PABA also induced down-regulation of NAT1 activity in several human cell lines grown at confluence. Substrate-dependent downregulation was not restricted to PABA. Addition of other NAT1 substrates, such as p-aminosalicylic acid, ethyl-p-aminobenzoate, or p-aminophenol to peripheral blood mononuclear cells in culture also resulted in significant (P < .05) decreases in NAT1 activity. However, addition of the NAT2-selective substrates sulfamethazine, dapsone, or procainamide did not alter NAT1 activity. Western blot analysis using a NAT1-specific antibody showed that the loss of NAT1 activity was associated with a parallel reduction in the amount of NAT1 protein (r(2) = 0.95). Arylamines that did not decrease NAT1 activity did not alter NAT1 protein levels. Semiquantitative reverse transcriptase polymerase chain reaction of mRNA isolated from treated and untreated cells revealed no effect of PABA on NAT1 mRNA levels. We conclude that NAT1 can be down-regulated by arylamines that are themselves NAT1 substrates. Because NAT1 is involved in the detoxification/activation of various drugs and carcinogens, substrate-dependent regulation may have important consequences with regard to drug toxicity and cancer risk.

Inactivation of human arylamine N-acetyltransferase 1 by the hydroxylamine of p-aminobenzoic acid

Human N-acetyltransferase 1 (NAT1) is a widely distributed enzyme that catalyses the acetylation of arylamine and hydrazine drugs as well as several known carcinogens, and so its levels in the body may have toxicological importance with regard to drug toxicity and cancer risk. Recently, we showed that p-aminobenzoic acid (PABA) was able to down-regulate human NAT1 in cultured cells, but the exact mechanism by which PABA acts remains unclear. In the present study, we investigated the possibility that PABA-induced down-regulation involves its metabolism to N-OH-PABA, since N-OH-AAF functions as an irreversible inhibitor of hamster and rat NAT1. We show here that N-OH-PABA irreversibly inactivates human NAT1 both in cultured cells and cell cytosols in a time- and concentration-dependent manner. Maximal inactivation in cultured cells occurred within 4 hr of treatment, with a concentration of 30 muM reducing activity by 60 +/- 7%. Dialysis studies showed that inactivation was irreversible, and cofactor (acetyl coenzyme A) but not substrate (PABA) completely protected against inactivation, indicating involvement of the cofactor-binding site. In agreement with these data, kinetic studies revealed a 4-fold increase in cofactor K-m, but no change in substrate K-m for N-OH-PABA-treated cytosols compared to control. We conclude that N-OH-PABA decreases NAT1 activity by a direct interaction with the enzyme and appears to be a result of covalent modification at the cofactor-binding site. This is in contrast to our findings for PABA, which appears to reduce NAT1 activity by down-regulating the enzyme, leading to a decrease in NAT1 protein content. BIOCHEM PHARMACOL 60;12: 1829-1836, 2000. (C) 2000 Elsevier Science Inc.

Photosensitization of the sunscreen octyl p-dimethylaminobenzoate by UVA in human melanocytes but not in keratinocytes

Sunscreens penetrate human epidermis and modify the biology of proliferating cells. This study addressed the question whether the UV response of cultured human cells is affected by direct treatment with nontoxic levels of sunscreens. Cell survival following exposure to UVC or unfiltered UVB was not altered by preincubation with 25 μg/mL of octyl p-dimethylaminobenzoate (o-PABA), 2-ethylhexyl p-methoxycinnamate (EHMC) or oxybenzone. However, UVA or UVB filtered to reproduce the solar UV spectrum penetrating to the basal layer of the epidermis, highly sensitized cells to killing by o-PABA but not by its hydrolysis product, 4-dimethylaminobenzoic acid. Sensitization was found in all cell types tested, except normal keratinocytes, and could be prevented by certain antioxidants particularly pyruvate and the hydroxyl radical scavenger mannitol. o-PABA and EHMC applied without UV reduced the adherence of cells. The results indicate that sunscreens may increase cell mobility and the combination of o-PABA with solar UV may selectively damage melanocytes in the skin.

Ensaios de terapêutica no Tifo exantemático neotrópico no Brasil

Die Auctoren stellten Untersuchungen an ueber die Heil- und Preventhivtherapie gegen den neo-tropischen Flecktyphus in Brasilien. Als Heilmittel gelangten zur Anwendung PABA (Para-amino-Benzolsaeure), Chlorofenol, Guanamidina, Aureomycin, Chloromiceten, Pas oder Para-amino-salicilico-Saeure, Streptomicina, Aralen und Paludrina. Als Preventivmittel benutzten sie den von der Drogarie Butantan in S. Paulo gelieferten Impfstoff. Vor allem empfehlen sie den Gebrauch von Aureomycin in geeigneten Dosen, selbst in schweren Faellen, und dann in Verbindung mit Chloromicetin. Betreffs der Preventivmittel halten sie es fuer verfrueht aus der Impfung eine dfinitive Folgerung zu ziehen.

Principales transformaciones en la vida cotidiana de la cabecera municipal de Chiriguaná, Cesar, producidas por la explotación del carbón a partir de la década de los 90. Estudio de Caso

En el centro del departamento del Cesar, se encuentra un municipio que podría ser una perfecta analogía del Macondo de García Márquez. Cuenta la historia de cómo se transforman sus humildes casas en ¿mansiones¿, sus viejas bicicletas en carros últimos modelo, las calles llenas de polvo en grandes avenidas pavimentadas, donde se cambió el ¿sancocho¿ por comidas sofisticadas, la estadía en la casa de un amigo por un hotel. Donde la iglesia, la devoción por la virgen de Chiquinquirá, un hospital municipal a medio dotar, un notario único, la Caja Agraria y un juzgado hacían parte de la estructura social del pueblo. Luego vinieron las regalías, contratos, y burocracia. Un pueblo que cuenta la historia de cómo existen grandes duchas en sus nuevas casas, pero no hay agua. Donde existen grandes televisores para ver películas, pero no hay luz, donde se han adjudicado millonarios contratos para la construcción de un alcantarillado que no ha sido terminado. Una mega biblioteca a punto de caerse, los estancos llenos, las cantinas llenas, dónde todo extranjero es costeño en carnavales o en las fiestas del ocho de septiembre. Los campesinos aún trabajan en parcelas, los pescadores aún venden desde la madrugada, un mercado que sigue funcionando desde las 3 de la mañana, un comercio de tiendas paisas. Un pueblo lleno de contrastes, pero sobre todo, con la responsabilidad de tener dentro de su jurisdicción uno de los proyectos mineros más rentables del país. Este municipio Macondiano se llama: Chiriguaná.

Metodologías de valoración de empresas

La valoración de una empresa como sistema dinámico es bastante compleja, los diferentes modelos o métodos de valoración son una aproximación teórica y por consiguiente simplificadora de la realidad. Dichos modelos, se aproximan mediante supuestos o premisas estadísticas que nos permiten hacer dicha simplificación, ejemplos de estos, son el comportamiento del inversionista o la eficiencia del mercado. Bajo el marco de un mercado emergente, este proceso presenta de indistinta forma retos paracualquier método de valoración, dado a que el mercado no obedece a los paradigmas tradicionales. Lo anterior hace referencia a que la valoración es aún más compleja, dado que los inversionistas se enfrentan a mayores riesgos y obstáculos. Así mismo, a medida que las economías se globalizan y el capital es más móvil, la valoración tomaráaún más importancia en el contexto citado. Este trabajo de gradopretende recopilar y analizar los diferentes métodos de valoración, además de identificar y aplicar aquellos que se reconocen como “buenas prácticas”. Este proceso se llevó a cabo para una de las empresas más importantes de Colombia, donde fundamentalmente se consideró el contexto de mercado emergente y específicamente el sector petrolero, como criterios para la aplicación del tradicional DCF y el práctico R&V.

Removal of sunscreen compounds from swimming pool water using self-organized TiO2 nanotubular array electrodes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determinação de parâmetros físico-químicos com um sensor potenciométrico sensível ao íon p-aminobenzoato

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Selective UV-filter detection with sensors based on stainless steel electrodes modified with polyaniline doped with metal tetrasulfonated phthalocyanine films

This work describes the construction and application of two amperometric sensors for sensitive UV-filter determination. The sensors were prepared using stainless steel electrodes in which polyaniline (PANI) was electrochemically polymerized in the presence of nickel (NiPcTS) or iron (FePcTS) tetrasulfonated phthalocyanines. The sensor surface characterizations were carried out using atomic force microscopy (AFM). The PANI/NiPcTS sensor was selective for the chemical UV-filter p-aminobenzoic acid (PABA) and the PANI/FePcTS sensor was selective for octyldimethyl-PABA (ODP), both in a mixture of tetrahydrofuran (THF) and 0.1 mol L(-1) H(2)SO(4) at a volume ratio of 30 : 70, and with an applied potential of 0.0 mV vs. Ag vertical bar AgCl. A detailed investigation of the selectivity was carried out for both sensors, in order to determine their responses for ten different UV filters. Finally, each sensor was successfully applied to PABA or ODP quantification in sunscreen formulations and water from swimming pools.

Nanopartículas de sílica e ácido p-amino benzóico: um estudo de associação para protetores solares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da radiação UV -B na interação Botrytis cinerea – clonostachys rosea em morangueiro e do ácido 4 - aminobenzóico no controle do patógeno em tabaco

Pós-graduação em Agronomia (Proteção de Plantas) - FCA

National Diet and Nutrition Survey: assessment of dietary sodium in adults (19 to 64 years) in England, 2014

There is an established relationship between salt intake and risk of high blood pressure (BP). High blood pressure (hypertension) is a risk factor for cardiovascular disease (CVD) and scientific evidence shows that a high salt intake can contribute to the development of elevated blood pressure. The Scientific Advisory Committee on Nutrition (SACN) recommend a target reduction in the average salt intake of the population to no more than 6g per day. This figure has been adopted by the UK government as the recommended maximum salt intake for adults and children aged 11 years and over. Following publication of the SACN report in 2003, the government began a programme of reformulation work with the food industry aimed at reducing the salt content of processed food products. Voluntary salt reduction targets were first set in 2006, and subsequently in 2009, 2011 and 2014, for a range of food categories that contribute the most to the population’s salt intakes. Population representative urinary sodium data were collected in England in 2005-06, 2008 (UK), 2011 and 2014. In the latest survey assessment, estimated salt intake of adults aged 19 to 64 years in England was assessed from 24-hour urinary sodium excretion of 689 adults, selected to be representative of this section of the population. Estimated salt intake was calculated using the equation 17.1mmol of sodium = 1g of salt and assumes all sodium was derived from salt. The data were validated as representing daily intake by checking completeness of the urine collections by the para-amino benzoic acid (PABA) method. Urine samples were collected over five months (May to September) in 2014, concurrently with a similar survey in Scotland. This report presents the results for the latest survey assessment (2014) and a new analysis of the trend in estimated salt intake over time. The trend analysis is based on data for urinary sodium excretion from this survey and previous sodium surveys (including data from the National Diet and Nutrition Survey Rolling Programme (NDNS RP) Years 1 to 5) carried out in England over the last ten years, between 2005-06 and 2014. This data has been adjusted to take account of biases resulting from differences between surveys in laboratory analytical methods used for sodium. The analysis provides a revised assessment of the trend in estimated salt intake over time. The trend analysis in this report supersedes the trend analysis published in the report of the 2011 England urinary sodium survey.