Differential Contribution of Albumin and Lipids to the Hydrophobic Extraction of Bis-(2-ethylhexyl) Phthalate from Hemodialysis Tubing by Human Serum: Analysis by Gas Chromatography - Stable Isotope Dilution Mass Spectrometry

Abstract

A method is presented which allows quantitative assignment of hydrophobic human serum components to the extraction of bis-(2-ethylhexyl) phthalate (DEHP) from medical tubing. Under optimized conditions (sample pH 5.5; fluid-fluid extraction with ethyl acetate + tert-butyl methyl ether 1 + 1 v/v; DEHP-ring-D4 as internal standard with ratios of endogenous (m/z = 149) and added deuterated DEHP (m/z = 153) adjusted to around 1.0; equilibration of added internal standard with the hydrophobic sample for 24 hours), a high precision can be achieved with an intra-assay coefficient of variation of 1.5% (n = 7) for sample DEHP quantification. Phthalate migration from hemodialysis tubing was quantified by use of a peristaltic pump and recirculation (200 minutes) of serum with different degrces of hypertriglyceridemia (range from 2.26 to 14.5 g/L) or solutions of human albumin (10 to 50 g/L). Only DEHP, but no other phthalates are detected in the extracts. There exist linear relations between DEHP extraction and triglyceride content (increase by 1.01 μg DEHP/g tubing material per g triglyceride/L serum) as well as between DEHP extraction and albumin content (0.59 μg DEHP/g tubing material per g albumin/L). Under physiological conditions, the total amount of albumin extracts 17.7-fold more DEHP than the total triglyceride amount in human serum. The suitability of the proposed method as a candidate reference method as well as consequences for dyslipidemic and hypalbuminemic patients on hemodialysis schemes are discussed.     

Transformation matrices as tool to investigate the changes in the electronic structure of reacting molecules along the reaction coordinate

The calculation of the transformation matrix between the molecular orbitals of the transition state and the educt provides detailed information on the alteration and interaction of the MO’s along the reaction coordinate. This is demonstrated for four different kinds of reactions: (a) Conrotatory ringopening of cyclobutene; (b) Addition of methylene to ethylene; (c) Nucleophilic substitution of CH₃CN and CH₃NC by CN⁻; (d) 1,2 Rearrangement of methylcarbene to ethylene. MNDO has been employed for the calculations but any other method may be used as well.     

The first 6′-O-sulfated phenylanthraquinones: isolation from Bulbine frutescens, structural elucidation, enantiomeric purity, and partial synthesis

From the roots of Bulbine frutescens, the first sulfated phenylanthraquinones were isolated, together with their known sulfate-free analogs. Their structures were elucidated by spectroscopic and chiroptical methods, by acid hydrolysis or by partial synthesis. The new compounds have the usual stereo-orientation at the biaryl axis (i.e., with the acetyl portion above the anthraquinone plane) except for sodium ent-knipholone 6′-O-sulfate (and thus, also its hydrolysis product, ent-knipholone), which exhibit an opposite axial configuration. We also describe the first stereoanalysis of natural phenylanthraquinones, some of which were found to be not enantiomerically pure, some even near-racemic. We furthermore, report on the first X-ray structure analysis of a phenylanthraquinone, viz. 4′-O-demethylknipholone.     

The excitation of radial resonances in a gas-filled tube

Summary The behaviour of radial resonances is interpreted and discussed with the help of boundary layer considerations.

---

Zusammenfassung Das Verhalten von radialen Resonanzen wird mit Hilfe von Grenzschicht-Betrachtungen gedeutet und diskutiert.

---

---

Dedicated to Professor Hans Thomann, on his fiftieth birthday     

Fluorescence diagnosis of bladder cancer with new water soluble hypericin bound to polyvinylpyrrolidone: PVP-hypericin

Although conventional white light endoscopy (WLE) is currently the gold standard for diagnosing bladder tumors, rates of false negative results and residual tumors after transurethral resection are relatively high. The goal of the present clinical study is to investigate whether using new water soluble hypericin (PVP-hypericin) as a fluorescent dye improves bladder cancer detection and diagnosis. Following instillation of PVP-hypericin (total amount of 0.25 mg hypericin bound to 25 mg polyvinylpoyrrolidone [PVP], reconstituted in 50 mL phys. sodium chloride solution), WLE and fluorescence cystoscopy (photodynamic diagnosis; PDD) were performed on patients with suspected primary or recurrent bladder malignancies (n = 57). Incubation time was 1-2 h and biopsies (n = 163) were taken from fluorescing regions and/or from regions which were suspicious under WLE. Histological investigations of the biopsies provided the final proof of malignancy (or the counterevidence). Results indicated that overall sensitivity with PVP-hypericin and PDD is significantly higher (95%) than with WLE (85%). The sensitivity of PDD in the diagnosis of carcinoma in situ (n = 12) was 100% compared with 33% for WLE. In the diagnosis of dysplasia, the sensitivity of PDD was 85% compared with 31% for WLE. PDD has a positive predictive value (PPV) of 0.75% and a negative predictive value (NPV) of 0.86%, in comparison to WLE PPV = 0.66% NPV = 0.58%. Biopsies were not taken from healthy tissues, thus specificity was markedly lower in our study (53%) than that reported in other studies (98-100%). As a conclusion, PDD using PVP-hypericin is superior to WLE in terms of sensitivity in the diagnosis of malignancies of the bladder. Results suggest that PVP-hypericin is a promising formulation for various diagnostic and therapeutic applications.     

Entrance effects at nanopores of nanocapsules functionalized with poly(ethylene glycol) and their flow through nanochannels

We studied the effect of poly(ethylene glycol) (PEG) on the extrusion of large, multilamellar nanocapsules (also called liposomes or vesicles) through nanochannels with a length of 6 microm. For the generation of the nanocapsules, we used a lipid mixture with lecithin consisting of saturated and unsaturated fatty acids (dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC)), cholesterol, and 2-8 mol % PEG linked to a lipid anchor (distearoylphosphatidylethanolamine (DSPE)) or the plain lipid anchor without PEG. An increase in PEG leads to a decrease of the critical tension for nanocapsule rupture (lysis tension) between 20-30%, whereas the pure lipid anchor does not produce any differences. We interpret these findings to be produced by a partial intrusion of the polymeric chain into the phospholipid bilayer of the nanocapsule which weakens its tensile strength. We evaluate statistically the discrepancies of lysis tensions found for different channels widths (50-100 nm) and two or four channels in series. Comparing our results on the flow resistance of either nanocapsules or pure water with lubrication theory, we find that the calculated viscous forces are not sufficient to account for the measured friction of nanocapsules. This shows that the nanocapsules are decelerated in the nanochannels by van der Waals interactions between channel and capsule walls and the intermediate water layer. The strength of these forces is 24 times higher for PEG and 94 times higher for the pure lipid anchor than the respective calculated viscous forces alone, showing that nanocapsule flow in nanochannels cannot be considered under the classical continuum assumption of the intermediate water layer.