Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1

Dipeptidyl peptidase IV (DPP IV) is the primary inactivator of glucoregulatory incretin hormones. This has lead to development of DPP IV inhibitors as a new class of agents for the treatment of type 2 diabetes. Recent reports indicate that other antidiabetic drugs, such as metformin, may also have inhibitory effects on DPP IV activity. In this investigation we show that high concentrations of several antidiabetic drug classes, namely thiazolidinediones, sulphonylureas, meglitinides and morphilinoguanides can inhibit DPP IV The strongest inhibitor nateglinide, the insulin-releasing meglitinide was effective at low therapeutically relevant concentrations as low as 25 mu mol/l. Nateglinide also prevented the degradation of glucagon-like peptide-1 (GLP-1) by DPP IV in a time and concentration-dependent manner. In vitro nateglinide and GLP-1 effects on insulin release were additive. In vivo nateglinide improved the glucose-lowering and insulin-releasing activity of GLP-1 in obese-diabetic ob/ob mice. This was accompanied by significantly enhanced circulating concentrations of active GLP-1(7-36)amide and lower levels of DPP IV activity. Nateglinide similarly benefited the glucose and insulin responses to feeding in ob/ob mice and such actions were abolished by coadministration of exendin(9-39) and (Pro(3))GIP to block incretin hormone action. These data indicate that the use of nateglinide as a prandial insulin-releasing agent may partly rely on inhibition of GLP-1 degradation as well as beta-cell K-ATP channel inhibition. (C) 2007 Elsevier B.V. All rights reserved.

Evaluation of Gas Solubility Prediction in Ionic Liquids using COSMOthermX

As the range of available ionic liquids increases, methods by which important engineering parameters such as gas solubilities can be estimated from simple structural information become ever more desirable. COSMO-based thermodynamic models, such as that used by COSMOthermX, allow the determination of such data for pure and mixed component systems. Herein, we evaluate the predictive capability of COSMOthermX through a comparison with literature data obtained from the IUPAC database which contains data for 15 gases in 27 ionic liquids, To determine any effect inherent to ionic liquids, gas solubility predictions were first performed for selected molecular solvents at constant temperature and pressure. Further estimations of gas solubility at temperatures ranging from (278 to 368) K at 0.1 MPa in water were performed for 14 gases. The Study has demonstrated that COSMOthermX is capable of predicting, qualitatively, gas solubilities in ionic liquids and, hence, reducing the amount of unnecessary experimental measurements prior to specific applications using ionic liquids.

Stable isomorphism of dual operator spaces

We prove that two dual operator spaces $X$ and $Y$ are stably isomorphic if and only if there exist completely isometric normal representations $phi$ and $psi$ of $X$ and $Y$, respectively, and ternary rings of operators $M_1, M_2$ such that $phi (X)= [M_2^*psi (Y)M_1]^{-w^*}$ and $psi (Y)=[M_2phi (X)M_1^*].$ We prove that this is equivalent to certain canonical dual operator algebras associated with the operator spaces being stably isomorphic. We apply these operator space results to prove that certain dual operator algebras are stably isomorphic if and only if they are isomorphic. We provide examples motivated by CSL algebra theory.

Foxp3+ T cells induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes.

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

Foraging ecology, fluctuating food availability and energetics of wintering brent geese

Changing energy requirements and dramatic shifts in food availability are major factors driving behaviour and distribution of herbivores. We investigate this in wintering East Canadian High Arctic light-bellied brent geese Branta bernicla hrota in Northern Ireland. They followed a sequential pattern of habitat use, feeding on intertidal Zostera spp. in autumn and early winter before moving to predominantly saltmarsh and farmland in late winter and early spring. Night-time feeding occurred throughout and made a considerable contribution to the birds' daily energy budget, at times accounting for > 50% of energy intake. Nocturnal feeding, however, is limited to the intertidal, possibly because of predation risk on terrestrial habitat, and increases with moonlight. The amount of Zostera spp., declined dramatically after the arrival of birds, predominantly, but not entirely, due to consumption by the birds. Birds gained fat reserves in the first 2 months but then this was dramatically lost as their major food source collapsed and their daily energy intake declined. Single birds consistently fared worse than paired birds and pairs with juveniles fared better than those without suggesting a benefit of having a family to compete for food. Many birds leave the Lough at this time of reduced Zostera spp. for other sea inlets in Ireland but some remain. Body condition of the latter gradually improved in early spring and reflected a heavy reliance on terrestrial habitats, particularly farmland, to meet the birds' daily energy requirements. However, even in the period immediately before migration to the breeding ground, the birds did not regain the amount of abdominal fatness observed in November. The dramatic changes in available food and requirements of the birds drive the major changes seen in foraging behaviour as the birds evade starvation in the wintering period.

Expedient synthesis of (+)-trans-5-allylhexahydroindolizidin-3-one

Treatment of the bicyclic iminium ion derived from 5-methoxyhexahydroindolizidin-3-one with allyltrimethylsilane gave exclusively the diastereoisomer in which the allyl group was axial. This substrate is a useful precursor to 5-propyl-3-alkylindolizidine alkaloids. (C) 1999 Elsevier Science Ltd. All rights reserved.

Barrier height variations and interface properties of PtSi/Si structures

To study some of the interfacial properties of PtSi/Si diodes, Schottky structures were fabricated on (100) crystalline silicon substrates by conventional thermal evaporation of Pt on Si followed by annealing at different temperatures (from 400 degrees C to 700 degrees C) to form PtSi. The PtSi/n-Si diodes, all yielded Schottky barrier (SB) heights that are remarkably temperature dependent. The temperature range (20-290 K) over which the I-V characteristics were measured in the present study is broader with a much lower limit (20 K), than what is usually reported in literature. These variations in the barrier height are adequately interpreted by introducing spatial inhomogeneity into the barrier potential with a Gaussian distribution having a mean barrier of 0.76 eV and a standard deviation of 30 meV. Multi-frequency capacitance-voltage measurements suggest that the barrier is primarily controlled by the properties of the silicide-silicon interface. The forward C-V characteristics, in particular, show small peaks at low frequencies that can be ascribed to interface states rather than to a series resistance effect.