Non-steroidal anti-inflammatory drugs may modulate the protease activity of Candida albicans

The phenotypic pressure exerted by non-steroidal anti-inflammatory drugs (NSAIDs) on autochthonous and pathogenic microbiota remains sparsely known. In this study, we investigated if some NSAIDs increment or diminish the secretion of aspartyl-proteases (Sap) by Candida albicans grown under different phenotypes and oxygen availability using a set of SAP knock-out mutants and other set for genes (EFG1 and CPH1) that codify transcription factors involved in filamentation and protease secretion. Preconditioned cells were grown under planktonic and biofilm phenotypes, in normoxia and anoxia, in the presence of plasma concentrations of acetylsalicylic acid, diclofenac, indomethacin, nimesulide, piroxicam, ibuprofen, and acetaminophen. For diclofenac, indomethacin, nimesulide, and piroxicam the secretion rates of Sap by SAP1-6, EFG1. and CPH1 mutants were similar or, even, inferior to parental wildtype strain. This suggests that neither Sap 1-6 isoenzymes nor Efg1/Cph1 pathways may be entirely responsible for protease release when exposed to these NSAIDs. Ibuprofen and acetaminophen enhanced Sap secretion rates in three environmental conditions (normoxic biofilm, normoxic planktonic and anoxic planktonic). In other hand, aspirin seems to reduce the Sap-related pathogenic behavior of candidal biofilms. Modulation of Sap activity may occur according to candidal phenotypic state, oxygen availability, and type of NSAID to which the cells are exposed. (C) 2010 Elsevier Ltd. All rights reserved.

Inhibition of C6 rat glioma proliferation by [Ru(2)Cl(Ibp)(4)] depends on changes in p21, p27, Bax/Bcl2 ratio and mitochondrial membrane potential

The ruthenium compound [Ru(2)Cl(Ibp)(4)] (or RuIbp) has been reported to cause significantly greater inhibition of C6 glioma cell proliferation than the parent HIbp. The present study determined the effects of 0-72 h exposure to RuIbp upon C6 cell cycle distribution, mitochondrial membrane potential, reactive species generation and mRNA and protein expression of E2F1, cyclin D1, c-myc, pRb, p21, p27, p53, Ku70, Ku80, Bax, Bcl2, cyclooxygenase 1 and 2 (COX1 and COX2). The most significant changes in mRNA and protein expression were seen for the cyclin-dependent kinase inhibitors p21 and p27 which were both increased (p<0.05). The marked decrease in mitochondrial membrane potential (p<0.01) and modest increase in apoptosis was accompanied by a decrease in anti-apoptotic Bcl2 expression and an increase in pro-apoptotic Bax expression (p<0.05). Interestingly, COX1 expression was increased in response to a significant loss of prostaglandin E(2) production (p<0.001), most likely due to the intracellular action of Ibp. Future studies will investigate the efficacy of this novel ruthenium-ibuprofen complex in human glioma cell lines in vitro and both rat and human glioma cells growing under orthotopic conditions in vivo. (C) 2010 Elsevier Inc. All rights reserved.

Estudo in silico da interação da albumina de soro humano com o ibuprofeno

Currently, computational methods have been increasingly used to aid in the characterization of molecular biological systems, especially when they relevant to human health. Ibuprofen is a nonsteroidal antiinflammatory or broadband use in the clinic. Once in the bloodstream, most of ibuprofen is linked to human serum albumin, the major protein of blood plasma, decreasing its bioavailability and requiring larger doses to produce its antiinflamatory action. This study aimes to characterize, through the interaction energy, how is the binding of ibuprofen to albumin and to establish what are the main amino acids and molecular interactions involved in the process. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant ε = 40 was used. The findings corroborate the literature in which the Sudlow site I (I-FA3) is the primary binding site and the site I-FA6 as secondary site. However, it differs in identifying the most important amino acids, which by interaction energy, in order of decreasing energy, are: Arg410, Lys414, Ser 489, Leu453 and Tyr411 to the I-Site FA3 and Leu481, Ser480, Lys351, Val482 and Arg209 to the site I-FA6. The quantification of interaction energy and description of the most important amino acids opens new avenues for studies aiming at manipulating the structure of ibuprofen, in order to decrease its interaction with albumin, and consequently increase its distribution

Avaliação de efeitos biológicos de antiinflamatórios derivados do ácido propiônico através de modelos experimentais em nível molecular e celular

Derivatives of propionic acid NSAIDs are irreversible inhibitors of cyclooxygenase enzyme widely used. The aim of this study was to evaluate, through different experimental models, biological effects of derivatives of propionic acid (fenoprofen, naproxen, ibuprofen and ketoprofen) in cellular and molecular level. The labeling of blood constituents with technetium-99m (99mTc) and morphological analysis of erythrocytes of blood of rats, as well as growth, survival of cultures of Escherichia coli (E. coli) and the assessment of bacterial plasmid electrophoretic profiles were models used for experimental evaluation of possible biological effects of antiinflammatory drugs. The results show that, in general, anti-inflammatory drugs evaluated were not able to alter the labeling of blood constituents with 99mTc, the morphology of red blood cells from blood of rats, as well as the growth of cultures of E. coli and the electrophoretic profile of plasmid DNA. However, naproxen appears to cytotoxic effect on bacterial cultures, plasmids and genotoxic effects in reducing the action of stannous chloride in cultures of E. coli. The use of experimental fast performance and low cost was important for assessment of biological effects, contributing to a better understanding of the properties of propionic acid derivatives studied. anti-inflammatory, blood constituents, technetium-99m, stannous chloride, Escherichia coli; DNA

Remoção de diclofenaco, ibuprofeno, naproxeno e paracetamol em filtro ecológico seguido por filtro de carvão granular biologicamente ativado

O filtro ecológico representa uma promissora tecnologia de tratamento, em razão desta não necessitar da aplicação de produtos químicos, além de sua constatada eficiência. Nele, estabelece-se entre os seres vivos a relação de cadeia alimentar. Inicialmente uma matriz aquosa foi acrescida de quatro fármacos (diclofenaco, naproxeno, ibuprofeno e paracetamol) e posteriormente analisada por cromatografia líquida de alta eficiência para avaliar a remoção desses compostos pelo filtro ecológico seguido pelo filtro de carvão granular biologicamente ativado. Parâmetros, entre eles turbidez, coliformes totais e termotolerantes, cor aparente e cor verdadeira, foram mensurados para verificar a eficiência dos filtros. Houve remoção de 97,43% do diclofenaco, 85,03% do ibuprofeno: 94,11% do naproxeno e 84,07% do paracetamol.

Thermoanalytical study of some anti-inflammatory analgesic agents

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

Non-steroidal anti-inflammatory drugs may modulate the protease activity of Candida albicans

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Thermal decomposition of some analgesic agents

Thermogravimetry, derivative thermogravimetry (TG, DTG) and differential scanning calorimetry (DSC), were used to study the thermal behaviour of mefenamic acid, ibuprofen, acetaminophen, sodium diclofenac, phenylbutazone, dipyrone and salicylamide. The results led to thermal stability data and also to the interpretation concerning the thermal decomposition. © 1996 Akadémial Kiadó.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Excipientes de medicamentos e as informações da bula

Aim: To evaluate the presence of preservatives, dyes, sweeteners and flavouring substances in 73 pharmaceutical preparations of 35 medicines for oral administration, according to drug labeling information about the excipients. Methods: 35 medications were selected, both over-the-counter and prescription durgs, marketed in Brazil. The sample included: analgesic/antipyretic, antimicrobial, mucoregulatory, cough and cold, decongestant, antihistamine, bronchodilator, corticosteroid, antiinflammatory and vitamin medications. We collected data on 73 preparations of these drugs, according to drug labeling information regarding preservatives, dyes, sweeteners and flavourings. Results: Methylparaben and propylparaben were the most common preservatives found (43% and 35.6% respectively). The most common sweeteners were: sucrose (sugar) (53.4%), sodium saccharin (38.3%) and sorbitol (36.9%). Twenty-one medicines (28,7%) contained two sweeteners. Colourless medicines predominated (43.8%), followed by those with sunset yellow dye (FD&C yellow no. 6) (15%). Five products (6.8%) contained more than one colour agent. Tartrazine (FD&C yellow no. 5) was present in seven preparations (9.5%). Fruit was the most common flavouring found (83%). Labelings of drugs which contained sugar frequently omitted its exact concentration (77%). Of the four labelings of medicines which contained aspartame, two did not warn patients regarding phenylketonuria. Conclusions: Omission and inacuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Complications of inadvertent intake of sugar-containing medicines by diabetics, or aspartame intake by patients with phenylketonuria may also occur.

Acesso a medicamentos essenciais em farmácias e drogarias do Município de Araraquara

A survey to determine the availability of 20 essential medicines for the diseases with highest prevalence in primary health care was conducted in the city of Araraquara. The presence and the price of these medicines in private sector pharmacies and drugstores of the city were recorded. Two forms, recommended by the WHO, were used in the survey, one for availability and the other for prices. The drugs most commonly available in pharmacies and drugstores were: propranolol (90.5%), captopril (96%) and ranitidine (96%), while the least available were ferrous sulfate (27%), beclomethasone (33.8%) and ibuprofen (41.9%). The drugs that showed the greatest variation among the prices charged were: propranolol (97.1%), hydrochlorothiazide (96.4%) and glibenclamide (95.0%), while the least variable were salbutamol (30.8%) and trimethoprim-sulfamethoxazole (30.2%). Generic drugs, which were half (10) of those assessed, had the lowest prices. The indicators of access, referring to the ability of patients to acquire drugs for the treatment of major diseases at the primary health care level, showed that no establishment stocked all 20 essential drugs and that wide variations existed in their prices, undermining their availability to drug users, whose only sources are pharmacies and drugstores. These data demonstrate the importance of the popular pharmacy to improve the access to medicines, by lowering the cost and increasing the availability of the items selected for the National List of Essential Drugs (RENAME).

Recent applications of analytical techniques for quantitative pharmaceutical analysis: A review

The intension of this paper was to review and discuss some of the current quantitative analytical procedures which are used for quality control of pharmaceutical products. The selected papers were organized according to the analytical technique employed. Several techniques like ultraviolet/visible spectrophotometry, fluorimetry, titrimetry, electroanalytical techniques, chromatographic methods (thin-layer chromatography, gas chromatography and high-performance liquid chromatography), capillary electrophoresis and vibrational spectroscopies are the main techniques that have been used for the quantitative analysis of pharmaceutical compounds. In conclusion, although simple techniques such as UV/VIS spectrophotometry and TLC are still extensively employed, HPLC is the most popular instrumental technique used for the analysis of pharmaceuticals. Besides, a review of recent works in the area of pharmaceutical analysis showed a trend in the application of techniques increasingly rapid such as ultra performance liquid chromatography and the use of sensitive and specific detectors as mass spectrometers.

Ocorrência de compostos farmacológicos no Córrego da Onça, município de Três Lagoas - MS

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da remoção de compostos farmacológicos em filtros de carvão granular biologicamente ativado em escala de laboratório

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da remoção de compostos farmacológicos em filtro ecológico seguido por filtro de carvão granular biologicamente ativado

Pós-graduação em Engenharia Civil - FEIS