Fernanda Martins

The intestinal permeation of didanosine from granules containing microspheres using the everted gut sac model

The aim of this research is to evaluate the intestinal permeation of a new formulation (NF) for the anti-retroviral didanosine (ddI) drug, using the everted gut sac model. The NF is composed by granules containing ddI incorporated in chitosan microspheres, plus free chitosan as an excipient. The permeation was evaluated across the three intestinal segments of adult male Wistar rats. The performance of ddI permeation from the NF was compared to the same granules without free chitosan and to buffered ddI tablets as control. The permeations across duodenum were higher than across jejune and ileum. The ddI from NF presented higher permeation and a crescent-shaped profile in duodenum compared to the other formulations. Such effects are provided by the superior mucoadhesiveness to the intestinal membrane and potentialize sustained release properties for NF. These results lead one to consider the novel formulation to be promising for ddI administration by oral route.

Reaction of [Os3(CO)10(MeCN)2] with 2,3-bis(2-pyridyl)pyrazine and pyrazyne. Synthesis, characterization and electrochemical behavior of 1:1 and 1:2 ligand:cluster complexes

Abstract The diimine-bridged, bis-triosmium carbonyl complexes [{Os 3 (CO) 10 ( μ -H)} 2 (pyz)] 1b , [{Os 3 (CO) 10 } 2 (dpp)] 2b , (pyz=pyrazine; dpp=2,3-bis(2-pyridyl)pyrazine) and their corresponding 1:1 ligand:cluster complexes [Os 3 (CO) 10 ( μ -H)(pyz)], 1a , [Os 3 (CO) 10 (dpp)], 2a , were synthesized by the reaction of [Os 3 (CO) 10 (MeCN) 2 ] with pyz and dpp ligands. All compounds were characterized by IR, 1 H-NMR spectroscopy and elemental analysis. Electrochemistry was used to examine the redox properties of 1 – 2 and of complexes [Os 3 (CO) 10 ( μ -H)(py)], 3 , for comparison purposes. The electrochemical behavior of the bridged bis-triosmium species 1b – 2b provided strong evidence for the electronic interaction between the two metal centers.

PEGylation of phospholipids improves their intermembrane exchange ratePresented at the 17th Conference of the European Colloid & Interface Science Society, Firenze, Italy, September 21?26, 2003.

The polar headgroup of dimyristoylphosphatidylethanolamine (DMPE) was modified by attaching a hydrophilic polymer-amino acid complex and the effects of this modification on the non-protein-mediated transfer features of the lipid determined. The first step in the organic synthesis protocol was the conversion of α,ω-dicarboxy poly(ethylene glycol) into its anhydride form, followed by attachment of the molecule to the amino group of DMPE. In the second step, the remaining free –COOH group on the polymer terminus was activated consecutively with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and sulfo-N-hydroxysuccinimide, and then coupled to tryptophan. The purified conjugate was mixed with dipentadecanoylphosphatidylglycerol (1/9 molar ratio) and sonicated to produce small unilamellar vesicles. These vesicles (donors) were then mixed with dipentadecanoylphosphatidylglycerol magnetoliposomes (acceptors) and the transfer kinetics of the modified lipid followed, using high-gradient magnetophoresis as the fractionation technique. The transfer behavior of non-modified DMPE was also examined. The first-order kinetic plots, corrected for back exchange lipid movement, showed that hydrophilization of DMPE dramatically improved its transfer capacity. These findings are explained by considering the thermodynamical consequences of the exchange process. The possibility of using biomolecule-derivatized phospholipids to trigger physiological effects in biological cells is briefly discussed.

Adsorption Isotherms of Mucin on Granules Containing Chitosan Microspheres

The effect of the excipients used for the preparation of granules containing chitosan microspheres on the adsorption of the muco-polysaccharide mucin was studied. Adsorption isotherms at 37°C were obtained as one strategy for the in vitro evaluation of the muco-adhesive properties of granules carrying drugs. The microspheres were prepared via an ionotropic gelation technique using sodium tripolyphosphate as the cross-linking agent. The resulting microspheres were dried at 40°C until a water content of 75% was achieved and the subsequent extrusion/spherulation process carried out using different excipients, i.e. unmodified chitosan, pre-gelated starch or carboxymethylcellulose. The Langmuir adsorption equation gave a good fit to the experimental data. Mucin exhibited the best affinity to granules containing chitosan as the excipient. Such granules also appeared to have the best muco-adhesive properties.

Suspected infection in afebrile patients: Are they septic?

Abstract We prospectively evaluated afebrile patients admitted to an emergency department (ED), with suspected infection and only tachycardia or tachypnea. The white blood cell count (WBC) was obtained, and patients were considered septic if leukocyte count was >12,000 &mgr;L–1 or <4000 &mgr;L–1 or with >10% of band forms. Clinical data were collected to examine whether sepsis could be predicted. Seventy patients were included and 37 (52.86%) met sepsis criteria. Self-measured fever showed an odds ratio (OR) of 5.936 (CI95% 1.450–24.295; P = 0.0133) and increased pulse pressure (PP) showed an OR of 1.405 (CI95% 1.004–1.964; P = 0.0471) on multivariate analysis. When vital signs were included in multivariate analysis, the heart rate showed an OR of 2.112 (CI95% 1.400–3.188; P = 0.0004). Self-measured fever and mean arterial pressure <70 mm Hg had high positive likelihood ratios (3.86 and 2.08, respectively). The nomogram for self-measured fever showed an increase of sepsis chance from 53% (pretest) to approximately 80% (post-test). The recognition of self-measured fever, increased PP, and the intensity of heart rate response may improve sepsis recognition in afebrile patients with tachycardia or tachypnea. These results are important for medical assessment of sepsis in remote areas, crowded and low-resourced EDs, and low-income countries, where WBC may not be readily available.