Identification of beta-cell-trophin, a peptide of the pituitary pars intermedia which stimulates insulin secretion in plasma from genetically obese (ob/ob) mice.

The influence of plasma from genetically obese (ob/ob) and lean (+/+) mice on insulin secretion has been studied by perifusion of collagenase-prepared pancreatic islets maintained for 48 h in culture. Insulin secretion was measured at 2-min intervals and plasma from the ob/ob mice not from the +/+ mice rapidly stimulated insulin release, reaching a maximum in 2-4 min and falling to basal levels in about 10 min. Experimental evidence is given indicating that the plasma insulin secretagogue is identical to beta-cell-trophin, a peptide of the pituitary pars intermedia which stimulates insulin secretion. The evidence is based on (1) the antigenic properties of the peptides (both cross-react with a -COOH terminal ACTH antiserum raised to the 17-39 moiety of ACTH), (2) identical chromatographic separation on Biogel columns and on reverse-phase high pressure liquid chromatography and (3) the similarity of their insulin releasing action from perifused islets.

Experimental procedure for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry.

A simple methodology for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry is presented to enable individuals to undertake such work in a routine clinical environment. Samples of PAG were irradiated using a linear accelerator and imaged using a 0.5 T (22 MHz) Philips Gyroscan MRI scanner. The mean spin-lattice relaxation rate was measured using a 'turbo-mixed' sequence, consisting of a series of 90 degrees pulses, each followed by acquisition of a train of spin echoes. The mean sensitivity for five different batches of PAG in the range up to 10 Gy was calculated to be 0.0285 s-1 Gy-1 for the mean spin-lattice relaxation rate with a percentage standard deviation of 1.25%. The overall reproducibility between batches was calculated to be 2.69%. This methodology, which introduces the novel use of pre-filled nitrogen vials for calibration, has been used to develop techniques for filling anatomically shaped anthropomorphic phantoms.

Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs.

Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs.

Well-defined sulfobetaine-based statistical copolymers as potential antibioadherent coatings.

The potential use of novel poly(sulfobetaine) copolymers as antibioadherent coatings was investigated using Pseudomonas aeruginosa as a model microorganism and human macrophages and 3T3 mouse embryonic fibroblasts. Two well-defined statistical copolymers with narrow molecular weight distributions were prepared by group transfer copolymerization of n-butyl methacrylate (nBuMA) with either 10 or 30 mol % 2-(dimethylamino)ethyl methacrylate (DMAEMA). Sulfobetainized nBuMA-DMAEMA copolymers (poly[sulfobetaine-stat-nBuMA]) were obtained by treating these precursor polymers with 1,3-propanesultone under mild conditions. Both proton NMR spectroscopy and elemental microanalyses indicated that essentially all the DMAEMA residues were derivatized in both copolymers. Poly(methyl methacrylate) (PMMA) discs were coated with the sulfobetainized nBuMA-DMAEMA copolymers and the bioadherent properties of these coated materials were compared with those of PMMA. Statistically significantly fewer (p<.05) bacteria, macrophages, and fibroblasts adhered to the poly(sulfobetaine-stat-nBuMA)-coated PMMA than to the uncoated PMMA. The poly(sulfobetaine-stat-nBuMA) copolymer containing the higher proportion (30 mol %) sulfobetainized DMAEMA residues proved to be the more effective antibioadherent coating. The antibioadherent properties of these coating materials may allow the cost-effective production of dirt-resistant, easy to clean work surfaces, bioinert coatings for medical devices, and antifouling coatings for marine, agricultural, and industrial applications.