Preparation, Characterisation and Measurement of the in vitro Cytotoxicity of Mesoporous Silica Nanoparticles Loaded with Cytotoxic Pt(II) Oxadiazoline Complexes

Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular carrier materials that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively unpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C,H,N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage

Entropies for complex systems: generalized-generalized entropies

Many complex systems are characterized by non-Boltzmann distribution functions of their statistical variables. If one wants to -- justified or not -- hold on to the maximum entropy principle for complex statistical systems (non-Boltzmann) we demonstrate how the corresponding entropy has to look like, given the form of the corresponding distribution functions. By two natural assumptions that (i) the maximum entropy principle should hold and that (ii) entropy should describe the correct thermodynamics of a system (which produces non-Boltzmann distributions) the existence of a class of fully consistent entropies can be deduced. Classical Boltzmann-Gibbs entropy is recovered as a special case for the observed distribution being the exponential, Tsallis entropy is the special case for q-exponential observations.Comment: CTNEXT 07, no fig

Vorelsterzeitliche Karsttaschen mit Terra-fusca-Füllung in der Kreide von Meerdorf im Landkreis Braunschweig

Bei Meerdorf im Landkreis Braunschweig finden sich auf der Oberfläche von mergeligen Kalken der Mucronatenschichten sack- und trichterförmige Taschen, die bis 3 m tief und mit braunem Ton und Geschiebesanden gefüllt sind. Auf schwacher Hangneigung gelegene Taschen sind in ihrem oberen Teil hangabwärts verzerrt und unter Fließschutt der Kreidekalke zu langen Schwänzen ausgezogen. Der braune Ton ist auch außerhalb der Taschen auf der narbigen Oberfläche der Kalke verbreitet, wogegen die Geschiebesande auf die Kerne der Taschen beschränkt sind. Über diesen Bildungen liegt eine Grundmoräne. Die Kleinformen der Kreideoberfläche und die tieferen Taschen sind durch Auflösung von Mergelkalkstein entstanden; der nichtkarbonatische Rückstand bildet eine Terra fusca. Die Verkarstung vollzog sich unter warmem Klima und begann möglicherweise schon vor dem Pleistozän. Die Geschiebesande in den Taschen sind vermutlich elsterzeitlich und waren ursprünglich flächenhaft verbreitet; in das Innere der Taschen sind sie durch Eiskeilbildung oder auf andere Weise gelangt. Danach wurden die Sande flächenhaft abgetragen. Deformiert wurden die Taschen zu Beginn der Saalezeit durch Solifluktion. Die das Profil abschließende Grundmoräne ist die des drenthestadialen Eisvorstoßes.researc

Impact of network structure on the capacity of wireless multihop ad hoc communication

As a representative of a complex technological system, so-called wireless multihop ad hoc communication networks are discussed. They represent an infrastructure-less generalization of todays wireless cellular phone networks. Lacking a central control authority, the ad hoc nodes have to coordinate themselves such that the overall network performs in an optimal way. A performance indicator is the end-to-end throughput capacity. Various models, generating differing ad hoc network structure via differing transmission power assignments, are constructed and characterized. They serve as input for a generic data traffic simulation as well as some semi-analytic estimations. The latter reveal that due to the most-critical-node effect the end-to-end throughput capacity sensitively depends on the underlying network structure, resulting in differing scaling laws with respect to network size.Comment: 30 pages, to be published in Physica

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a –N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states

Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma

Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity

Smart antimicrobial efficacy employing pH-sensitive ZnO-doped diamond-like carbon coatings

One of the main challenges in endoprosthesis surgeries are implant-associated infections and aseptic-loosenings, caused by wear debris. To combat these problems, the requirements to surfaces of endoprostheses are wear-resistance, low cytotoxicity and antimicrobial efficacy. We here present antimicrobial coatings with a smart, adaptive release of metal ions in case of infection, based on ZnO-nanoparticles embedded in diamond-like carbon (DLC). The Zn2+ ion release of these coatings in aqueous environments reacts and adapts smartly on inflammations accompanied by acidosis. Moreover, we show that this increased ion release comes along with an increased toxicity to fibroblastic cells (L929) and bacteria (Staphylococcus aureus subsp. aureus, resistant to methicillin and oxacillin. (ATCC 43300, MRSA) and Staphylococcus epidermidis (ATCC 35984, S. epidermidis). Interestingly, the antimicrobial effect and the cytotoxicity of the coatings increase with a reduction of the pH value from 7.4 to 6.4, but not further to pH 5.4