Interaction of naproxen amphiphilic derivatives with biomembrane models evaluated by differential scanning calorimetry and Langmuir-Blodgett studies

Anti-inflammatory drugs represent a potential new strategy for the treatment of Alzheimer's disease (AD). The ability to cross the blood-brain barrier and to reach brain tissues is a critical point for these drugs and is strictly related to their lipophilicity. Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAIDs) under active investigation for AD. To improve its lipophilic character, NAP was conjugated through a diethylamine spacer (EDA) to lipoamino acids (LAA), α-amino acids containing a long alkyl side chain, to obtain the NAP-EDA-LAA10 and NAP-EDA-LAA14 prodrugs. The interaction of NAP and prodrugs with dimyristoylphosphatidylcholine phospholipids, forming either multilamellar vesicles or monolayers (at the air/water interface) and used as biomembrane models, was studied by differential scanning calorimetry and Langmuir-Blodgett techniques. Experimental data showed that NAP conjugation with LAA residues was able to enhance the drug interaction with such biomembrane models.     

Characterization of foxing stains in early twentieth century photographic and paper materials

Abstract

The subject of this present work is a group of nine historical pictures shot in Palermo by the Sicilian photographer E. Interguglielmi in 1912. They are nine matte-collodion prints mounted on the original cardboard supports and all of them show foxing stains affecting the paper surface. In order to characterise the chemical composition of the supports and investigate foxing spots, non-destructive and micro-destructive analysis were carried out. X-rays fluorescence (XRF) analysis was used to characterise the elemental composition of all the mounting boards, allowing a comparison between the foxing spots and non-affected areas. Laser-Induced Breakdown Spectroscopy was used to investigate the presence of lower atomic number elements, not detectable by XRF, while SEM imaging allowed the investigation of surface appearance and nature of original paper samples from the cardboards.     

The influence of daylight exposure on platelet 5-HT levels in patients with major depression and schizophrenia

Platelet serotonin (5-HT) can be used as a limited, peripheral model for the central 5-HT synaptosomes. Altered platelet 5-HT concentrations have been associated with psychiatric disorders like depression and schizophrenia. The aim of the present study was to compare platelet 5-HT concentrations during long, medium and short period of natural daylight exposure in a large number of medication-free male and female schizophrenic and depressed patients and sex-matched healthy controls. Platelet 5-HT concentration was determined spectrofluorimetrically in 240 (97 female, 143 male) schizophrenic and 258 (153 female, 105 male) nonpsychotic, nonsuicidal depressed medication-free patients and 328 (149 women, 179 men) healthy subjects during periods with short (<12), long (>12) and medium (average 12) hours of the natural daylight. Platelet 5-HT concentration was significantly lower in women compared to men in all groups. Healthy male subjects had significantly higher (p=0.011) platelet 5-HT concentrations during long compared to medium period. There were no significant differences (p>0.05) in platelet 5-HT concentration between different periods in healthy women. The significant increase in platelet 5-HT values were found in female (p=0.01) and male (p=0.029) depressed patients during long compared to short period. There were no significant associations between platelet 5-HT concentrations and different periods in both male and female schizophrenic patients. The results indicate the sex-related differences in the serotonergic system. The alterations of platelet 5-HT concentrations, observed across period with different durations of daylight exposure, point to a direct or indirect effect of light on peripheral 5-HT system that could be related to different sensitivity of the pineal gland to light and/or melatonin influence on 5-HT metabolism.     

Calorimetric evaluation of the interaction and absorption of eicosapentaenoic acid by biomembrane models

The interaction of eicosapentaenoic acid, a polyunsaturated fatty acid belonging to the omega-3 class, with biomembrane models represented by multilamellar or unilamellar vesicles made of dimyristoylphosphatidylcholine was monitored by means of differential scanning calorimetry technique. The calorimetric analysis of vesicle prepared in the presence of increasing molar fraction of eicosapentaenoic acid was carried out to show its maximum interaction with biomembrane models evaluating the effects of eicosapentaenoic acid on the biomembrane models thermotropic parameters (transition temperature and enthalpy variation). Furthermore, in order to detect the influence of the presence of hydrophilic or lipophilic media on the entity of the compound absorption by the biomembrane models, kinetic experiments were carried out.The results indicate that eicosapentaenoic acid strongly interacts with the biomembrane models depressing the transition temperature and the enthalpy variation. Eicosapentaenoic acid is absorbed by the biomembrane models and the absorption is affected by the used medium; in fact a bigger absorption happens in the presence of a lipophilic medium.     

Adaptation of NS cells growth and differentiation to high-throughput screening-compatible plates

Background  

There is an urgent need of neuronal cell models to be applied to high-throughput screening settings while recapitulating physiological and/or pathological events occurring in the Central Nervous System (CNS). Stem cells offer a great opportunity in this direction since their self renewal capacity allows for large scale expansion. Protocols for directed differentiation also promise to generate populations of biochemically homogenous neuronal progenies. NS (Neural Stem) cells are a novel population of stem cells that undergo symmetric cell division in monolayer and chemically defined media, while remaining highly neurogenic.     

Enhancement of gemcitabine affinity for biomembranes by conjugation with squalene: differential scanning calorimetry and Langmuir-Blodgett studies using biomembrane models

Molecular interactions between gemcitabine, alone or conjugated with squalene to form the gem-squalene prodrug, with dimyristoylphosphatidylcholine have been investigated by differential scanning calorimetry and Langmuir film balance techniques to gain information about the interaction of gemcitabine and its prodrug with mammalian cell membranes and to evaluate the potential of liposomes as a delivery system for gemcitabine prodrugs. Phospholipids assembled as multilamellar vesicles or monolayers (at the air water interface) have been used as biomembrane models. Different interactions of gemcitabine, its prodrug, and squalene with the lipid were detected by dispersing the compounds in the MLV and were compared with kinetic experiments carried out to consider the ability of the examined compounds to dissolve in an aqueous medium, to migrate through it, and to be captured by multilamellar vesicles. Their ability to be released from drug-loaded liposomes and be taken up by empty vesicles mimicking biomembranes was also considered. Analysis of the differential scanning calorimetry curves reveals that gemcitabine has very little interaction with multilamellar vesicles whereas the gem-squalene prodrug strongly interacts with multilamellar vesicles. The kinetic experiments suggest that an aqueous medium does not permit the prodrug uptake by the biomembrane models, whereas it is allowed when gem-squalene is gradually released by the liposomes. The molecular area/surface pressure isotherms of the gemcitabine/lipid, gem-squalene/lipid, and pure compound monolayers, in agreement with the calorimetric results, indicate that gem-squalene interacts with the phospholipid monolayer with the squalene moiety in contact with the phospholipid chains and gemcitabine protruding in the aqueous medium.     

Ein Beitrag zur Kenntnis der Biogenese der Sialinsäure

Zusammenfassung Die Konzentrationen der Brenztraubensäure und der Eiweißzuckerkomponenten wurden in 150 Seren, deren Struktur im Sinne eines deutlichen Anstiegs der-Globulinfraktionen verändert war, ohne Rücksicht auf die Ätiologie dieser Dysprotoeinämien, ermittelt.Aus den Resultaten ist ersichtlich, daß sich am Stoffwechsel der Kohlenhydratkomponenten der Eiweißzucker auch die Brenztraubensäure beteiligt. Aus einem Vergleich der Mittelwerte der genannten Konzentrationen bzw. deren Indices geht hervor, daß zwischen dem Anstieg der Konzentration der Brenztraubensäure und des Hexosamins einerseits, der der Sialinsäure anderseits eine Beziehung besteht. Dies bekräftigt die Annahme, daß auch die Biosynthese der Sialinsäure über die Brenztraubensäure und das Hexosamin ablaufen könnte.

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Summary The concentrations of pyruvic acid and the protein sugar components were determined in 150 sera, whose structure was altered in the sense of a pronounced increase in the-globulin fractions, without consideration of the etiology of these dysproteinemias.It can be seen from the findings that pyruvic acid is also a participant in the metabolism of the carbohydrate components of the protein sugars. From a comparison of the mean values of the cited concentrations or their indices it may be concluded that a relation exists between the rise in the concentration of the pyruvic acid and of the hexosamine on one hand and that of the sialinic acid on the other. This supports the assumption that the biosynthesis of the sialinic acid also can proceed via pyruvic acid and hexosamine.

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Résumé On a déterminé les concentrations en acide pyruvique et en glucoprotéides de 150 sérums dont la structure était altérée par une augmentation importante en-globulines, sans prendre en considération l'étiologie de ces dysprotéinémies.Les résultats montrent clairement que l'acide pyruvique participe aussi à l'assimilation des constituants hydrocarbonés des glucoprotéides. La comparaison des valeurs moyennes des concentrations en question met en évidence une relation entre l'augmentation de la concentration en acide pyruvique et en hexosamine d'une part et celle de l'acide sialinique d'autre part. Ceci renforce l'hypothèse que la biosynthèse de l'acide sialinique pourrait aussi découler via l'acide pyruvique et à l'hexosamine.

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Herrn Prof. Dr. Ing.Fritz Feigl zum 70. Geburtstag gewidmet.     

Quantitative determination of acetylsalicylic acid in commercial drugs using DSC

In this article, the quantitative determination of acetylsalicylic acid (ASA) contained in two of the most commercially available pharmaceutical formulations was performed using differential scanning calorimetry (DSC) after a thermoanalytical characterization and a preliminary test on compatibility of ASA with three of the most commonly considered excipients [cellulose (CE), starch (ST) and sodium saccharin (SS)]. Finally, the analytical results obtained were compared with those derived by titrimetry and two UV spectrophotometric methods: i.e. a ‘direct method’ and a method based on first-order derivative UV spectra.     

Solid–liquid phase diagrams of binary mixtures

This study investigates the sorption of toluene and naphthalene by a sodium bentonite (BFN), an organoclay (WS35) and by their respective iron oxide hydrate composites Mag_BFN and Mag_S35. The organic matter content of WS35 and Mag_S35, determined by thermogravimetry, was used to obtain their organic matter sorption coefficients, which show that they are effective sorbents to remove organic contaminants from water, with a higher selectivity for naphthalene than for toluene sorption. The main iron oxide phase present in Mag_BFN and Mag_S35 is maghemite (γ-Fe₂O₃), which allows these sorbents to be separated from the effluent by a magnetic separation process after use.