Development of a sensitive potentiometric sensor for determination of fumaric acid in powdered food products

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

Synthesis, spectral and thermal studies on dicarboxylate-bridged palladium(II) coordination polymers. Part II

The synthesis and thermal behavior of the new [Pd(fum)(bipy)] (n) center dot 2nH(2)O (1), [Pd(fum)(bpe)] (n) center dot nH(2)O (2) and [Pd(fum)(pz)] (n) center dot 3nH(2)O (3) {bipy = 4,4'-bipyridine, bpe = 1,2-bis(4-pyridyl)ethene and pz = pyrazine} fumarate complexes are described in this work as well their characterization by IR and (13)C CPMAS NMR spectroscopies. TG curves showed that the compounds released organic ligands and lattice water molecules in the temperature range of 46-491 A degrees C. In all the cases, metallic palladium was identified as the final residue.

Contribuição do uso de medicamentos para a admissão hospitalar

According to the Word Health Organization, adverse drug reactions (ADR) are any harmful and non intentional answer which occurred in doses normally used in human beings. The ADR can be responsible for 2.4% to 11.5% of hospital admissions. Therefore, this study aimed at knowing the admitted patient's demographic profile due to possible ADR, identifying the most frequent drugs and complaints, and evaluating the incidence of hospital admission related to drug use. Patients who were 18 years old or more and were admitted during a period of one month to a medical clinical of a general hospital were interviewed for one month about drug use before being admitted, as well as regarding to the complaint which led them to hospital. These information were analyzed according to official data, like MICROMEDEX® and WHO criteria as well. It was observed that the admission due to drug use occurred in most part of the cases in elderly [47.5% (66/139)] and women [62% (87/139)]. The most frequent drugs used were: omeprazole (16), analgesics (31), antihypertensive (31), simvastatin (7) and formoterol fumarate (6), and the symptoms were normally associated to the digestive (20.5%), circulatory (20.2%), respiratory (18.2%) and central nervous systems (13.9%). It was estimated that 15.5% (139/897) of the hospital admission occurred possibly due to the drug use. The data found by present study suggests some strategies in order to prevent ADR in the context of primary health care services, such as monitoring drug therapy, manly for patients with chronic diseases, elderly and polimedicated people; and pharmaceutical care including dispensation and purchasing of the drugs, a lot of them dispensed over the counter (OTC).

Participation of genes involved in the process of anaerobic respiration of infection in chickens by salmonella typhimurium

Intestinal pathogens are exposed to various stress conditions during their infectious cycle. Anaerobiosis, one of such hostile condition, is offered by the host within gut and intestinal lumen, where survival, multiplication and entry into intestinal epithelial cells are priority for the invasion of the pathogen. The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)-trimethylamine N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHIJ) operons in Salmonella Typhimurium (STM) encode enzymes involved in anaerobic respiration to the electron acceptors fumarate, DMSO, TMAO, and nitrate, respectively. They are regulated in response to nitrate and oxygen availability and changes in cell growth rate. Vitamin B12 (cobalamin) is synthesized by Salmonella Typhimurium only under anaerobic growth conditions used as a cofactor in four known reactions. The deletion of cobS and cbiA genes prevent any form of cobalamin production. In the present study we evaluate the infection of birds by mutants of STM, with the anaerobic respiratory system committed by mutations in the genes: narG, napA, cobS, cbiA, frdA, dmsA, and torC. Virulence was assessed by oral inoculation of groups of one-day-old broilers with 0.1 mL of culture contained 10 8 colony forming units (CFU)/mL or diluted at 10 -3 and 10 -2 of strains mutants of Salmonella Typhimurium. Clinical signs and mortality were recorded over a period of 21 days. In general, the symptoms of chickens infected with the mutant strains were similar to those presenting by control birds. Except for STMNalr cbiA, all showed reduced capacity to cause mortality in comparison with the original strain. The mortality of group of chickens infected with STMNal r △narG, STMNal r △frdA, STMNal r △dmsA and STMNal r △cobS△cbiA showed significant decrease in mortality compared to control group (p<0.05).

Thermoanalytical study of heavier trivalent lanthanides fumarates

Solid-state heavier lanthanides fumarates compounds have been synthesized, and the compounds were characterized by employing simultaneous thermogravimetry and differential thermal analysis (TG-DTA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), TG coupled to FTIR, elemental analysis, and complexometry. On heating, the dehydration occurs in a single and two consecutive steps and the thermal decomposition of the anhydrous compounds occurs in consecutive and/or overlapping steps, with formation of the respective oxides: Tb4O7 and Ln2O3 (Ln=Dy to Lu). The results also led to information about composition, thermal behavior, and the type of coordination of the isolated compounds. © 2012 Akadémiai Kiadó, Budapest, Hungary.

Participação de genes associados ao processo de respiração anaeróbica na infecção de aves por Salmonella Typhimurium

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Síntese e caracterização de estruturas supramoleculares organizadas a partir de sistemas de paládio(II)/ácidos dicarboxílicos/ligantes lineares nitrogenados

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo sobre o uso do pentacloreto de nióbio, como ácido de Lewis, na síntese de enaminas através da reação de adição de Michael

The NbCl5 being a strong electrophile, is a potential candidate to act as a Lewis acid, and therefore it mediates various organic reactions. For this reason, it has received continuous attention by Brazilian researchers, especially in recent decades, since Brazil holds the largest reserves of niobium, besides being the largest producer of this element. The Michael addition reaction is one of the most widely used for forming carbon-carbon bonds and takes place by the addition of nucleophiles to activated olefins. Although this type of reaction is usually catalyzed by base, there are reports in the literature on the use of various Lewis acids in this type of reaction. The synthesis of enamines based acetilenodicarboxilates and amines, aromatic or alkyl, by Michael addition reaction is quite interesting, since these are valuable synthetic intermediates for the synthesis of heterocyclic and they are used in multicomponent reactions. The derivatives of anilino-fumarate also have a great potential for medical application. In this study we investigated the use of niobium pentachloride as Lewis acid to catalyze the Michael additions between the derivatives of aniline and acetilenodicarboxilates the synthesis of enamines

Produção de 1,3-propanodiol por Klebsiella pneumoniae e Escherichia coli: otimização de meio e clonagem de genes

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

Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Pro-phylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.

Particle emission from heavy-duty engine fuelled with blended diesel and biodiesel

In this study, particulate matter (PM) were characterized from a place impacted by heavy-duty vehicles (Bus Station) fuelled with diesel/biodiesel fuel blend (B3) in the city of Londrina, Brazil. Sixteen priority polycyclic aromatic hydrocarbons (PAH) concentrations were analyzed in the samples by their association with atmospheric PM, mass size distributions and major ions (fluorite, chloride, bromide, nitrate, phosphate, sulfate, nitrite, oxalate; fumarate, formate, succinate and acetate; lithium, sodium, potassium, magnesium, calcium and ammonium). Results indicate that major ions represented 21.2% particulate matter mass. Nitrate, sulfate, and ammonium, respectively, presented the highest concentration levels, indicating that biodiesel may also be a significant source for these ions, especially nitrate. Dibenzo[a,h]anthracene and indeno[1,2,3,-cd]pyrene were the main PAH found, and a higher fraction of PAH particles was found in diameters lower than 0.25 mu m in Londrina bus station. The fine and ultrafine particles were dominant among the PM evaluated, suggesting that biodiesel decreases the total PAH emission. However, it does also increase the fraction of fine and ultrafine particles when compared to diesel.

delta-Lactam derivative from thermophilic soil fungus exhibits in vitro anti-allergic activity

From cultures of thermophilic soil fungus Humicola grisea var thermoidea, a delta-lactam derivative (3-(2-(4-hydroxyphenyl)-2-oxoethyl)-5,6-dihydropyridin-2( 1H)-one) that displayed anti-allergic activity was isolated, which was predicted by in silico computational chemistry approaches. The in vitro anti-allergic activity was investigated by beta-hexosaminidase release assay in rat basophilic leukaemia RBL-2H3 cells. The delta-lactam derivative exhibited similar anti-allergic activity (IC50 = 18.7 +/- 6.7 mu M) in comparison with ketotifen fumarate (IC50 = 15.0 +/- 1.3 mu M) and stronger anti-allergic activity than azelastine (IC50 = 32.0 mu M). Also, the MTT cytotoxicity assay with RBL-2H3 cells showed that delta-lactam does not display cytotoxicity at concentrations lower than 50 mu M. This study suggests that the delta-lactam derivative has the potential to be used as a lead compound in the development of anti-allergic drugs for clinical use in humans.

Crystal structure of dihydroorotate dehydrogenase from Leishmania major

Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases. In this study, we report the crystal structures of DHODH from Leishmania major, the species of Leishmania associated with zoonotic cutaneous leishmaniasis, in its apo form and in complex with orotate and fumarate molecules. Both orotate and fumarate were found to bind to the same active site and exploit similar interactions, consistent with a ping-pong mechanism described for class 1A DHODHs. Analysis of LmDHODH structures reveals that rearrangements in the conformation of the catalytic loop have direct influence on the dimeric interface. This is the first structural evidence of a relationship between the dimeric form and the catalytic mechanism. According to our analysis, the high sequence and structural similarity observed among trypanosomatid DHODH suggest that a single strategy of structure-based inhibitor design can be used to validate DHODH as a druggable target against multiple neglected tropical diseases such as Leishmaniasis, Sleeping sickness and Chagas' diseases. (C) 2012 Elsevier Masson SAS. All rights reserved.

Aktivierung des Sauerstoffsensors FNR von Escherichia coli durch Glutathion in vivo und in vitro

Der Sauerstoffsensor FNR (Fumarat-Nitratreduktase-Regulator) von Escherichia coli spielt eine wichtige Rolle beim Umschalten vom aeroben zum anaeroben Stoffwechsel. FNR ist ein Transkriptionsregulator, der im aktiven Zustand ein [4Fe4S]-Zentrum besitzt. Bei Kontakt mit Sauerstoff zerfällt das [4Fe4S]- zu einem [2Fe2S]-Zentrum und führt zum Verlust der Aktivität von FNR. Die Reaktionen, die zum Aufbau des [4Fe4S]-Zentrums und der reduktiven Aktivierung von aerob und anaerob isoliertem apoFNR führen, wurden in vivo und in vitro untersucht. Die Einfluß in vivo von Glutathion auf die Funktion von FNR und die Rolle von Glutathion beim Aufbau des [4Fe4S]-Zentrums in gereinigtem apoFNR zeigen die wichtige Bedeutung von Glutathion bei der de novo Assemblierung von [4Fe4S]FNR und bei der reduktiven Aktivierung von sauerstoff-inaktiviertem FNR. Die energetischen Parameter von E. coli und ihre Änderungen beim Übergang vom aeroben zum anaeroben Stoffwechsel wurden untersucht. Das elektrochemische Protonenpotential delta-p über der Cytoplasmamembran wurde im Gleichgewichtszustand in der aeroben Atmung und anaeroben Nitrat-, Fumarat- und Dimethylsulfoxid-Atmung bestimmt. Delta-p betrug in der aeroben Atmung -160 mV, in der anaeroben Atmung sank delta-p entgegen früheren Vermutungen lediglich um 20 mV. Die geringen Änderungen von delta-p können deshalb vermutlich nicht als regulatorisches Signal für das Umschalten vom aeroben zum anaeroben Stoffwechsel genutzt werden.

Rekonstitution des Fumaratsensors DcuS in Liposomen und Transport von Fumarat und Succinat in Escherichia coli

Das Zweikomponentenregulationssystem DcuSR kontrolliert die Expression der wichtigsten fumaratinduzierten Gene in Escherichia coli. Die Gene dcuB und dctA, die fürDicarboxylatcarrier kodieren, sowie das Fumaratreduktase-Operon (frd), sind Zielgene für DcuSR. DcuS ist eine membranständige Sensorkinase mit einer großen periplasmatischen Domäne. NMR-spektroskopische Untersuchungen dieser Domäne zeigen Alpha-Helices und Beta-Faltblätter. Für die Fumaratbindung wichtige Aminosäuren wurden durch Mutagenese identifiziert. Gereinigtes DcuS wurde in Liposomen rekonstituiert. In Anwesenheit von ATP wird DcuS autophosphoryliert. Der Phosphatrest kann dann auf DcuR übertragen werden und beweist somit die Aktivität dieses in vitro Testsystems.Der Transport von C4-Dicarboxylaten erfolgt unter anaeroben Bedingungen durch die sekundären Carrier DcuA, DcuB und DcuC. Es konnte ein weiteres Protein (DcuD) identifiziert werden, das hohe Sequenzähnlichkeit zu DcuC aufweist. Eine dcuD-Mutante zeigte keinen Phänotyp und überproduziertes DcuD konnte den Ausfall der anderen Dcu-Carrier nicht kompensieren. DcuD ist damit ein kryptisches Mitglied der Dcu-Carrierfamilie. Unter aeroben Bedingungen katalysiert DctA den Transport von C4-Dicarboxylaten. Dennoch können dctA-Mutanten noch mit Succinat wachsen. Die Diffusionsrate von Succinat durch Membranen wurde bestimmt. Sie ist um Größenordnungen niedriger als der Transport in der Mutante. Bei dem DctA unabhängigen Transportsystem handelt es sich um einen H+/Succinat2-Symporter, der bei saurem pH aktiv ist und viele Eigenschaften eines Monocarboxylatcarriers aufweist.