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Barbosa A.F.,Federal University of Alfenas | Santos P.G.,Federal University of Alfenas | Lucho A.M.S.,Laboratory of Analytical Chemistry | Schneedorf J.M.,Federal University of Alfenas
Journal of Electroanalytical Chemistry

Kefiran, an exopolysaccharide isolated from kefir d'acqua grains, has anti-inflammatory and antimicrobial activities, however, a mechanism of action directly associated with biomembranes is not yet understood. The influence of kefiran on a l-α-Phosphatidylcholine/cholesterol supported bilayer lipid membrane using a Pt electrode was studied by voltammetry and electrochemical impedance spectroscopy. The interaction of the oligosaccharide with s-BLMs promoted the access of Fe(CN)63-/4- probe ions to the electrode surface. Kefiran was found to induce molecular pores at the s-BLM surface within 5 min at 11.4 μmol/L. The suggested mechanism seems to involve hydrogen bonding between the carbohydrate and the phosphate head group of the phospholipid with a carpet-like model of interaction. The overall results can be contributed to direct molecular interactions between the prebiotic oligosaccharides and the cell surfaces, which can be related to the biological activity of kefiran in several experimental models. © 2011 Elsevier B.V. All rights reserved. Source

Ortega-Deballon P.,University of Burgundy | Ortega-Deballon P.,University Hospital | Facy O.,University of Burgundy | Facy O.,University Hospital | And 8 more authors.
Annals of Surgical Oncology

Background. Hyperthermic intraperitoneal chemotherapy (HIPEC) achieves good results in selected patients with peritoneal carcinomatosis. There are two main procedures to deliver this therapy: the open abdomen and the closed abdomen techniques. A true comparison of the two techniques has never been performed. The aim of this study was to compare blood and abdominal tissue concentrations of oxaliplatin after open and closed techniques to deliver HIPEC. Methods. Nine pigs underwent HIPEC at 42-43°C for 30 min with oxaliplatin (400 mg/m2) according to two techniques: closed (three animals) or open (six animals). The open technique used either an external heater with a pump (three animals) or an intra-abdominal heating cable (three animals) to achieve hyperthermia. Temperature homogeneity, systemic absorption, and abdominal tissue mapping of the penetration of oxaliplatin with each technique were studied. Two additional pigs underwent hyperthermia with dyes instead of oxaliplatin to depict the distribution of the liquid within the abdomen with both techniques. Results. Hyperthermia was satisfactory with both techniques. The closed technique achieved higher temperatures within the diaphragmatic area, while the open technique obtained higher temperatures in the mid and lower abdomen (P<0.001 for both comparisons). The systemic absorption of oxaliplatin was higher with the open technique (P<0.04 for all comparisons), as was the accumulation within the abdominal cavity. The operating time for the two techniques was not greatly different. Conclusions. Intraperitoneal hyperthermia can be achieved with both techniques. The open technique had far higher systemic absorption and abdominal tissue penetration of oxaliplatin than the closed technique. © Society of Surgical Oncology 2010. Source

In recent years there has been considerable interest in the synthesis and separation of enantiomers of organic compounds especially because of their importance in the biochemistry and pharmaceutical industry. Major differences in biological activity have been observed in chiral molecules. These differences in stereochemistry can influence the pharmacological, metabolic or toxicological activity of the finished drug formulations. In other words isomer specific pharmaceuticals often exhibit increased potency, higher bioavailability and reduced side effects when compared to racemic pharmaceutical compounds. The development of new practical methods for the preparation of enantiomerically pure substances is thus vital and nowadays, pharmaceutical industry demands detailed investigations of chiral molecules, in compliance with the regulatory requirements. In this review some of the most important methods developed for the enantiomeric resolution by high pressure liquid chromatography, from the last decade, are described. The mechanisms of the different separation principles are briefly discussed. Also the major chiral stationary phases, commercially available, are presented, including a guide provided to help the readers selecting the appropriate chiral stationary phase. Finally the most common chiral selectors used as additives in mobile phases are described, including their advantages and their limitations. © 2010 Bentham Science Publishers Ltd. Source

Haufroid V.,Catholic University of Louvain | Haufroid V.,Laboratory of Analytical Chemistry
Current Drug Targets

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes, and act as efflux proteins. ABC transporters are characterised by the presence of genetic polymorphisms mainly represented by single nucleotide polymorphisms (SNPs), some of which having an impact on their activity. Besides physiological substances, drugs are also substrates of some ABC transporters, mainly ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2. Identifying the impact of these polymorphisms on the pharmacokinetics (PK) of these drugs may have important clinical implications, certainly for those characterised by a narrow therapeutic index and significant inter- and intra-patient PK variability. This review focuses specifically on ABCB1 and ABCC2 and critically analyses important publications dealing with the influence of ABCB1 and/or ABCC2 polymorphisms on drug disposition in humans. For different reasons discussed in this paper, the effect of ABCB1 and/or ABCC2 polymorphisms on drug concentrations in blood is not always easy to interpret and to correlate with pharmacological effects. In contrast, intracellular or target tissue drug concentrations appear more directly influenced by these polymorphisms, as illustrated with intralymphocyte concentrations for immunosupressants and antiretrovirals or with cerebrospinal fluid (CSF) concentrations for antiepileptics and antidepressants. Further research on intracellular and/or target tissue drug concentrations are still needed to better characterise the PK-PG (pharmacogenetics) relationship involving ABC transporters. © 2011 Bentham Science Publishers Ltd. Source

Miniero R.,Chemical Toxicology Unit | Beccaloni E.,Chemical Toxicology Unit | Carere M.,Chemical Toxicology Unit | Ubaldi A.,Laboratory of Analytical Chemistry | And 7 more authors.
Marine Pollution Bulletin

Total mercury (Hgtot) and methyl mercury (MeHg) were quantified in several specimens of Dicentrarchus labrax and Sparus aurata from the east basin of the Orbetello lagoon, central Italy. The size of each specimen was recorded to estimate body burdens (BBs); =Hgtot and MeHg were measured in fillets of both species. Hgtot and MeHg in S. aurata ranged between 0.355-1.58 and 0.341-1.53μg/g wet weight (ww), respectively; in D. labrax, their ranges were 0.284-2.54 and 0.214-2.35μg/g ww. Approximately 90% of the concentrations measured exceeded Hgtot regulatory maximum level of 0.5μg/g ww; however, exceedance rate was different in the two species studied. No correlations between specimen size and Hgtot or MeHg BBs were detected in this study. © 2013 Elsevier Ltd. Source

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