Unique molecular‐recognition microcapsules for environmental stimuli‐responsive controlled release have been developed. The microcapsules consist of a core–shell porous membrane. The pores contain ...linear‐grafted poly(NIPAM‐co‐BCAm) chains, which act as the molecular‐recognition gates. The Figure shows the mechanism of the opening of the pores to release the molecules inside.
To assess the pharmacokinetics, pharmacodynamics and safety of vildagliptin, a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-4), in Japanese patients with Type 2 diabetes.
In this ...randomized, double-blind, placebo-controlled, parallel-group study, 62 Japanese patients with Type 2 diabetes received vildagliptin 10 mg, 25 mg or 50 mg twice daily for 7 days. Blood samples were collected for the determination of plasma concentrations of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1), glucose, insulin and glucagon.
Exposure to vildagliptin (area under the plasma concentration-time curve from 0 to 12 h (AUC0-12h) and the maximum plasma concentration (Cmax)) increased in an approximately dose-proportional manner, and no accumulation was observed following multiple doses of vildagliptin (accumulation factor 1.00 - 1.02). DPP-4 activity was completely inhibited for varying durations by all doses of vildagliptin; the duration of complete DPP-4 inhibition was dose-dependent. DPP-4 inhibition after vildagliptin 50 mg twice daily remained > 80% throughout the 24-h period. Vildagliptin treatment led to a dose-dependent increase in plasma active GLP-1 levels; the overall increases (area under the effect-time course from 0 to 8 h, AUE0-8h) after 7 days' treatment were 1.5-, 1.7-, and 1.8-fold with vildagliptin 10 mg, 25 mg and 50 mg twice daily, respectively (all p < 0.0001 vs. placebo). Postprandial plasma glucose during the 4-h period after breakfast was significantly reduced with the 10, 25 and 50 mg vildagliptin doses by 50.3, 92.2 and 69.5 mg·h/dl, respectively. Insulin levels remained unchanged in the context of reduced glucose levels at all doses studied.
Vildagliptin demonstrated similar pharmacokinetic and pharmacodynamic effects in Japanese patients to those observed previously in non-Japanese patients with Type 2 diabetes.
The family of interferon-induced transmembrane protein (
Ifitm/mil/fragilis) genes encodes cell surface proteins that may modulate cell adhesion and influence cell differentiation. Mouse
Ifitm1 and
...-3, which are expressed in primordial germ cells (PGCs), are implicated to have roles in germ cell development, but the specific functions have been unclear. Our results show that
Ifitm1 activity is required for PGC transit from the mesoderm into the endoderm, and that it appears to act via a repulsive mechanism, such that PGCs avoid
Ifitm1-expressing tissues. In contrast,
Ifitm3, which is expressed in migratory PGCs, is sufficient to confer autonomous PGC-like homing properties to somatic cells. These guidance activities are mediated by the N-terminal extracellular domain of the specific IFITM, which cannot be substituted by that of another family member. Complex homo- and/or heterotypic intercellular interactions among various IFITMs in PGCs and neighboring cells may underpin coordinated germ cell guidance in mice.
Development of the mammalian nervous system involves generation of neurons from neural stem cells, migration of generated neurons toward genetically determined locations, extension of axons and ...dendrites, and establishment of neuronal connectivity. Recent progresses revealed diverse role of heparan sulfate proteoglycans in these processes. This article reviews our current knowledge about the functional roles of heparan sulfate proteoglycans in three critical events in mammalian neural development, namely neurogenesis, axon guidance, and synapse development.
Both thermoresponsive flat membranes and core‐shell microcapsule membranes, with a porous membrane substrate and grafted poly(N‐isopropylacrylamide) (PNIPAM) gates, were successfully prepared using a ...plasma‐graft pore‐filling polymerization method. PNIPAM was proven to be grafted homogeneously onto the porous membrane substrates, in the direction of both the membrane thickness and surface. Regardless of the solute molecular size, temperature had an opposite effect on diffusion coefficients of the solute across the PNIPAM‐grafted membranes with low graft yields as opposed to those with high graft yields. The PE‐g‐PNIPAM membranes change from positive thermo‐response to negative thermoresponse types with increasing pore‐filling ratios at around 30%. Phenomenological models were developed for predicting the diffusion coefficient of the solute across PNIPAM‐grafted membranes at temperatures, both above and below the lower critical solution temperature (LCST). Predicted diffusional coefficients of solutes across both the PNIPAM‐grafted flat and PNIPAM‐grafted microcapsule membranes fit the experimental values. To obtain an ideal result for the diffusional thermoresponsive controlled release through PNIPAM‐grafted membranes, the substrates strong enough to prevent any conformation changes are more suitable for preparing thermoresponsive membranes than weak ones.
Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to ...xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivarius agar for mutans streptococci and on blood agar for total culturable flora. At 5 wks, mutans streptococci levels in plaque were 10x lower than baseline in G3 and G4 (P = 0.007/0.003). There were no differences in saliva. At 6 mos, mutans streptococci in plaque for G3 and G4 remained 10x lower than baseline (P = 0.007/0.04). Saliva for G3 and G4 was lower than baseline by 8 to 9x (P = 0.011/0.038). Xylitol at 6.44 g/day and 10.32 g/day reduces mutans streptococci in plaque at 5 wks, and in plaque and unstimulated saliva at 6 mos. A plateau effect is suggested between 6.44 g and 10.32 g xylitol/day.
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