Theoretical study of enantiodifferentiation in solid state cyclodextrins

A molecular mechanics investigation of R- vs. S-phenylethanol, R- vs. S-mandelic acid, R- vs. S-flurbiprofen, and R- vs. S-fenoprofen in their cyclodextrin crystal environments was undertaken. It was found that the dominant force responsible for guesthost complexation is the short-range London force; the enantiodiscriminating forces tend to be very small and are generally, but not always, dominated by long-range electrostatic contributions. Derivatized cyclodextrins are generally more enantiodiscriminating than native cyclodextrins, perhaps due to exterior rather than interior guest-host binding. © 1993 Wiley-Liss, Inc.     

The distribution of galanin message-associated peptide-like immunoreactivity in the pig.

Using a radioimmunoassay (RIA) developed to the N-terminal part of the predicted sequence of porcine galanin message-associated peptide (GMAP), we have confirmed the existence of GMAP-like immunoreactivity (-LI) in normal porcine tissues. GMAP-LI was found to parallel the distribution of galanin-immunoreactivity (-IR), although consistently the concentrations detected were, on a molar ratio, significantly less than those measured for galanin throughout the gastrointestinal tract, brain, spinal cord, adrenal and pituitary gland. As cleavage of the prohormone would be expected to produce galanin and GMAP on an equimolar basis, it is possible that the endogenous, intact GMAP peptide does not fully cross-react with the antibody raised to the N-terminal GMAP sequence. Gel chromatography of tissue extracts revealed a single molecular form of galanin-IR in the gut and four distinct molecular forms in the adrenal gland. GMAP-LI eluted as a single immunoreactive component in the gut, and in the adrenal gland there were two major molecular forms, one of which was apparently also detected by the galanin assay, and a small amount of N-terminal fragment. This molecular heterogeneity seems likely to be a result of the various possible prohormone cleavage products and/or posttranslational processing modifications. Further analysis of the galanin gene products needs to be undertaken in order to confirm this.     

Advances in biomimetic collagen mineralisation and future approaches to bone tissue engineering

With an ageing world population and ~20% of adults in Europe being affected by bone diseases, there is an urgent need to develop advanced regenerative approaches and biomaterials capable to facilitate tissue regeneration while providing an adequate microenvironment for cells to thrive. As the main components of bone are collagen and apatite mineral, scientists in the tissue engineering field have attempted in combining these materials by using different biomimetic approaches to favour bone repair. Still, an ideal bone analogue capable of mimicking the distinct properties (i.e., mechanical properties, degradation rate, porosity, etc.) of cancellous bone is to be developed. This review seeks to sum up the current understanding of bone tissue mineralisation and structure while providing a critical outlook on the existing biomimetic strategies of mineralising collagen for bone tissue engineering applications, highlighting where gaps in knowledge exist.     

Parathyroid hormone (PTH) fragments relax the guinea-pig trachea in vitro

Synthetic bovine parathyroid hormone fragment containing the N-terminal 1-34 amino acids (bPTH-(1-34) ) relaxed the guinea-pig trachea constricted with histamine in vitro. Peptides with bovine and human sequences purchased from Peninsula Laboratories and Beckman Bioproducts produced similar effects. Substitution of methionine in positions 8 and 18 by norleucine did not affect this property of bPTH-(1-34). However, when the methionines were oxidized by treating the peptide with hydrogen peroxide, the peptide could no longer produce relaxation in the trachea. Oxidation of the methionine-replaced analog did not affect the action of the peptide on the trachea. It seems that the methionines per se are not necessary, but once oxidized the conformation of the molecule may be sufficiently altered to affect its ability to relax the trachea. While propranolol can block the relaxing action of isoproterenol, this blocking agent produces no inhibition of the bPTH-(1-34) effect. This action of PTH on the trachea may be related to cAMP because isobutyryl-methylxanthine, a phosphodiesterase inhibitor, potentiates and imidazole, a phosphodiesterase stimulator, inhibits the trachea relaxing action of bPTH-(1-34).     

Interplay effects during enhanced dynamic wedge deliveries

In this study the interplay effects for Enhanced Dynamic Wedge (EDW) treatments are experimentally investigated. Single and multiple field EDW plans for different wedge angles were delivered to a phantom and detector on a moving platform, with various periods, amplitudes for parallel and perpendicular motions. A four field 4D CT planned lung EDW treatment was delivered to a dummy tumor over four fractions. For the single field parallel case the amplitude and the period of motion both affect the interplay resulting in the appearance of a step function and penumbral cut off with the discrepancy worst where collimator-tumor speed is similar. For perpendicular motion the amplitude of tumor motion is the only dominant factor. For large wedge angle the dose discrepancy is more pronounced compared to the small wedge angle for the same field size and amplitude-period values. For a small field size i.e. 5 × 5 cm² the loss of wedged distribution was observed for both 60° and 15° wedge angles for parallel and perpendicular motions. Film results from 4D CT planned delivery displayed a mix of over and under dosages over 4 fractions, with the gamma pass rate of 40% for the averaged film image at 3%/1 mm DTA (Distance to Agreement). Amplitude and period of the tumor motion both affect the interplay for single and multi-field EDW treatments and for a limited (4 or 5) fraction delivery there is a possibility of non-averaging of the EDW interplay.