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A convenient chemo-enzymatic synthesis and (18)F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane.

Org Biomol Chem. 2008 Dec 21;6(24):4567-74

Authors: Riss PJ, Rösch F

The present report is concerned with a stereoselective, reliable route to trans-1,2-disubstituted cyclopropanes and in particular to (S,S)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane () and (R,R)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (ent-) as conformationally restricted, terminally fluorinated C(4)-building blocks for medicinal chemistry. The enzymatic kinetic resolution based synthesis of and ent- utilises inexpensive, commercially available starting materials. It is based on enantiomeric resolution of rac-cyclopropane carboxylic esters using esterase from Streptomyces diastatochromogenes. Both enantiomers of were prepared selectively in high overall yield over nine steps, starting from ethyl acrylate. The successful radiosynthesis of [(18)F]- and [(18)F]-ent- is also reported.

PMID: 19039365 [PubMed - in process]

Wall Shear Stress in Intracranial Self-Expanding Stents Studied Using Ultra-High-Resolution 3D Reconstructions.

AJNR Am J Neuroradiol. 2008 Nov 27;

Authors: Benndorf G, Ionescu M, Y Alvarado MV, Hipp J, Metcalfe R

BACKGROUND AND PURPOSE: Imaging of intracranial stents is constrained by resolution limits of current clinical imaging techniques providing insufficient visualization of deployment details and impeding its use for computational hemodynamic (CHD) simulations. The purpose of our study was to evaluate whether ultra-high-resolution MicroCT scans can illuminate detailed aspects of realistic in vitro stent deployment and serve as a reliable basis for CHD simulations of blood flow through self-expanding intracranial stents. MATERIALS AND METHODS: A Neuroform Treo (NF) stent and an Enterprise (ENT) stent were deployed in identical straight polytetrafluoroethylene tubes filled with contrast agent. MicroCT scans were obtained at a spatial resolution of 14 mum and used for ultra-high-resolution 3D reconstructions. CHD simulations were performed, with particular emphasis on local flow behavior near the wall and struts. Flow differences between the geometrically different stents were studied. RESULTS: MicroCT data revealed strut prolapse near the markers for the closed-cell design (ENT) stent and at some of the unconnected vertices of the open-cell design (NF) stent, which also showed some misalignments. CHD simulations showed that reverse wall shear stress occurred near some of the strut vertices and markers for the NF but only near the markers for the ENT. CONCLUSIONS: This work demonstrates the feasibility of ultra-high-resolution MicroCT imaging in elucidating important details of intracranial stent deployment as a basis for accurate CHD simulations and in enabling a structural and hemodynamic study of realistically deployed stents with different geometry and design.

PMID: 19039050 [PubMed - as supplied by publisher]

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Formulation of thermoresponsive and bioadhesive gel for treatment of oesophageal pain and inflammation.

Eur J Pharm Biopharm. 2008 Nov 12;

Authors: Makó A, Csóka G, Pásztor E, Marton S, Horvai G, Klebovich I

The aim of this study was the formulation and examination of a novel thermoresponsive and bioadhesive, in situ gelling drug delivery system, which can be used in the treatment of oesophageal pain and inflammation. A bioadhesive cellulose derivative (Metolose((R)) 60SH) was used as a thermoresponsive material, because Metolose((R)) has thermal gelation properties at certain temperature. The thermal gelation temperature (T(2)) of Metolose((R)) 60SH 2w/w% solution is above body temperature (65-66 degrees C), but by using different methods (Metolose((R)) 60SH concentration, auxiliary materials), it can be shifted near to body temperature. The pH alteration between pH=2-11 and the application of different alcohols did not influence the gelation temperature, but using water-soluble salts and changing the concentration of Metolose((R)) 60SH solution between 2 and 3w/w% the thermal gelation point could be decreased. Different NSAIDs were used as model drugs and which had not influence on thermal gelation temperature, but difference in in vitro liberation and penetration can be observed. In vitro adhesion test pointed out that the condition of investigated membrane can change the adhesion. Morphological test of oesophageal tissue showed that investigated materials had no irritative or tissue-damaging effect on the oesophageal mucosa even after 12h.

PMID: 19038337 [PubMed - as supplied by publisher]

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Tympanometric experiments on retracted ear drums - does tympanometry reflect the true middle ear pressure?

Acta Otolaryngol. 2008 Nov 27;:1-8

Authors: Wilhelm Pau H, Punke C, Just T

Conclusions: Tympanometry in ears with retracted or partially atelectatic tympanic membranes does not reflect the true middle ear (ME) pressure. The position of the tympanogram peak depends on the size of a retraction pocket and the remaining ME gas volume. Thus tympanometry in such cases cannot be used for measurements of ME pressure. Objective: To prove the hypothesis that tympanometry in ears with retraction pockets or atelectasis does not measure ME pressure correctly. Materials and methods: Tympanometry was performed in a simplified artificial ME model, in which different 'tympanic membranes' with pockets could be integrated. Results: We found a shift of the tympanogram peaks, either towards negative or positive pressures, depending on the position of the pocket: in case of an 'inward' direction (towards the ME like a retraction pocket) the peak was in the negative pressure range, in case of an 'outward' direction (bulging into the ear canal) the shift was towards positive pressures. The shift increased with decreasing volume behind the tympanic membrane. The effect cannot be simply be explained by hysteresis but by the air 'cushion' that is 'trapped' behind the membrane, limiting its excursions during the tympanometric sweep.

PMID: 19037824 [PubMed - as supplied by publisher]

The treatment of tongue haemangioma by plasma knife surgery.

Singapore Med J. 2008 Nov;49(11):e312-4

Authors: Kutluhan A, Bozdemir K, Ugras S

A seven-year-old girl presented with a 4 cm x 2 cm lesion of the tongue which was located at the posterior one-third in the midline. The lesion was excised by plasma knife surgery. No complication, such as bleeding, shortness of breath or infection, occurred after the treatment. Plasma knife surgery is an acceptable choice for selected benign lingual vascular malformations.

PMID: 19037538 [PubMed - in process]