Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases

Surface modified nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) cores surrounded by a chitosan and thiolated chitosan gel layer were prepared and characterized in previous works. The presence of such biopolymers on the nanoparticle surface conferred those nanosystems interesting characteristics that might partially overcome the gastrointestinal enzymatic barrier, improving the oral administration of pharmacologically active peptides. In the present work, the antiprotease behaviour of this family of core–shell nanoparticles was in vitro tested against two model metallopeptidases present in the gastrointestinal tract (GIT): Carboxypeptidase A -CP A- (luminal protease) and Leucine Aminopeptidase M -LAP M- (membrane protease). As previous step, the zinc-binding capacity of these nanoparticles was evaluated. Interestingly, an improvement of both the zinc-binding capacity and the antiprotease effect of chitosan was observed when the biopolymers (chitosan and thiolated chitosan) were used as coating component of the core–shell nanoparticles, in comparison with their behaviour in solution, thanks to the different biopolymer chains rearrangement. The presence of amino, hydroxyl and thiol groups on the nanoparticle surface promoted zinc binding and hence the inhibition of the metallopeptidases analysed. On the contrary, the occurrence of a cross-linked structure in the gel layer surrounding the PIBCA cores of thiolated formulations, due to the formation of interchain and intrachain disulphide bonds, partially limited the inhibition of the proteases. The low accessibility of cations to the active groups of the cross-linked polymeric shell was postulated as a possible explanation of this behaviour. Results obtained in this work make this family of surface-modified nanocarriers promising candidates for the successfull administration of pharmacologically active peptides and proteins by the oral route.     

A separation theorem and Serre duality for the Dolbeault cohomology

LetX be a complex manifold with finitely many ends such that each end is eitherq-concave or (n−q)-convex. If , then we prove thatH ^pn−q (X) is Hausdorff for allp. This is not true in general if (Rossi’s example withn=2 andq=1). If all ends areq-concave, then this is the classical Andreotti-Vesentini separation theorem (and holds also for ). Moreover the result was already known in the case when theq-concave ends can be ‘filled in’ (again also for ). To prove the result we first have to study Serre duality for the case of more general families of supports (instead of the family of all closed sets and the family of all compact sets) which is the main part of the paper. At the end we give an application to the extensibility of CR-forms of bidegree (p, q) from (n−q)-convex boundaries, . This research was partially supported by TMR Research Network ERBFMRXCT 98063.     

Changes in orcine muscle water characteristics during growth--an in vitro low-field NMR relaxation study

This study investigates the effects of developmental stage and muscle type on the mobility and distribution of water within skeletal muscles, using low-field (1)H-NMR transverse relaxation measurements in vitro on four different porcine muscles (M. longissimus dorsi, M. semitendinosus, M. biceps femoris, M. vastus intermedius) from a total of 48 pigs slaughtered at various weight classes between 25 kg and 150 kg. Principal component analysis (PCA) revealed effects of both slaughter weight and muscle type on the transverse relaxation decay. Independent of developmental stage and muscle type, distributed exponential analysis of the NMR T(2) relaxation data imparted the existence of three distinct water populations, T(2b), T(21), and T(22), with relaxation times of approximately 1-10, 45-120, and 200-500 ms, respectively. The most profound change during muscle growth was a shift toward faster relaxation in the intermediate time constant, T(21). It decreased by approx. 24% in all four muscle types during the period from 25 to 150 kg live weight. Determination of dry matter, fat, and protein content in the muscles showed that the changes in relaxation time of the intermediate time constant, T(21), during growth should be ascribed mainly to a change in protein content, as the protein content explained 77% of the variation in the T(21) time constant. Partial least squares (PLS) regression revealed validated correlations in the region of 0.58 to 0.77 between NMR transverse relaxation data and muscle development for all the four muscle types, which indicates that NMR relaxation measurements may be used in the prediction of muscle developmental stage.     

Engineering Aspects of Preparation of Nanocrystalline Particles in Microemulsions

Engineering aspects of the preparation of palladium nanoparticles in non-ionic w/o-microemulsions are examined. In order to achieve reproducible synthesis conditions a semi-batch reactor with a standardized design is used. Influences of the stirring rate and of different ways of concentration control on the product properties are observed. For reproducible synthesis it is important to establish appropriate and defined preparation conditions. Monodisperse palladium particles of around 5nm size are obtained by adding the microemulsion containing the palladium salt at a constant feed rate to the precharged microemulsion containing the reducing agent. A quantitative kinetic model is proposed to describe particle formation in microemulsions. Unknown parameters of the model have been estimated by independent examinations or can be achieved by fitting to the experimental data.     

Photometric method for the determination of nitrite in aqueous solutions and in blood

Summary The sensitivity of the hitherto known determinations of nitrite by formation of azo dyes and photometric measurement in aqueous solution is limited by the concentration of nitrite. In the method described here the azo compound formed is extracted into toluene and trichloroacetic acid is added to the extract. Immediately after addition of the latter the colour intensity reaches its maximum and is measured at 560 nm. In this way the sensitivity is made independent of the nitrite concentration in the aqueous solution and is limited only by the sample volume available.This study was supported by Deutsche Forschungsgemeinschaft.     

A linear algorithm for a core of a tree

A core of a graph G is a path P in G that is central with respect to the property of minimizing d(P) = Σ_υ?V(G)d(υ, P), where d(υ, P) is the distance from vertex υ to path P. We present a linear algorithm for finding a core of a tree. Since the core of a graph is not necessarily unique, we also output a list of all the vertices which are in some core.     

Reduction of β-ketosulfoxides : a highly efficient asymmetric synthesis of both enantiomers of methyl carbinols from the corresponding esters

It is shown that reductions of β-ketosulfoxides of identical chirality (R) at sulfur, lead to reduction products of opposite stereochemistry according to the reducing agent used. The high enantiomeric excesses obtained (80 to 100%) provide a general route to both enantiomers of methylcarbinols from the corresponding esters.