Measuring glucose at the site of insulin delivery with a redox-mediated sensor.

Automated insulin delivery systems for people with type 1 diabetes rely on an accurate subcutaneous glucose sensor and an infusion cannula that delivers insulin in response to measured glucose. Integrating the sensor with the infusion cannula would provide substantial benefit by reducing the number of devices inserted into subcutaneous tissue. We describe the sensor chemistry and a calibration algorithm to minimize impact of insulin delivery artifacts in a new glucose sensing cannula.

An Amperometric Glucose Sensor Integrated into an Insulin Delivery Cannula: In Vitro and In Vivo Evaluation.

Background: Labeling prohibits delivery of insulin at the site of subcutaneous continuous glucose monitoring (CGM). Integration of the sensing and insulin delivery functions into a single device would likely increase the usage of CGM in persons with type 1 diabetes.

Methods: To understand the nature of such interference, we measured glucose at the site of bolus insulin delivery in swine using a flexible electrode strip that was laminated to the outer wall of an insulin delivery cannula.

Role for Rab10 in Methamphetamine-Induced Behavior.

Lipid rafts are specialized, cholesterol-rich membrane compartments that help to organize transmembrane signaling by restricting or promoting interactions with subsets of the cellular proteome. The hypothesis driving this study was that identifying proteins whose relative abundance in rafts is altered by the abused psychostimulant methamphetamine would contribute to fully describing the pathways involved in acute and chronic effects of the drug. Using a detergent-free method for preparing rafts from rat brain striatal membranes, we identified density gradient fractions enriched in the raft protein flotillin but deficient in calnexin and the transferrin receptor, markers of non-raft membranes.

TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.

Tumor necrosis factor alpha (TNF-alpha) production is abnormally high in Fanconi anemia (FA) cells and contributes to the hematopoietic defects seen in FA complementation group C-deficient (Fancc(-/-)) mice. Applying gene expression microarray and proteomic methods to studies on FANCC-deficient cells we found that genes encoding proteins directly involved in ubiquitinylation are overrepresented in the signature of FA bone marrow cells and that ubiquitinylation profiles of FA-C and complemented cells were substantially different. Finding that Toll-like receptor 8 (TLR8) was one of the proteins ubiquitinylated only in mutant cells, we confirmed that TLR8 (or a TLR8-associated protein) is ubiquitinylated in mutant FA-C cells and that TNF-alpha production in mutant cells depended upon TLR8 and the canonical downstream signaling intermediates interleukin 1 receptor-associated kinase (IRAK) and IkappaB kinase-alpha/beta.

Induction of apoptosis by aryl-substituted diamines: role of aromatic group substituents and distance between nitrogens.

A series of aromatic substituted diamines was synthesized and characterized for their cytotoxic profiles against human breast and prostate tumor cell lines. Following a structure function analysis of the effects of changes of the benzyl substituents and the distance between amino groups the most potent analogues were analyzed biologically and were shown to induce apoptosis. These compounds do not induce the enzyme SSAT or deplete intracellular polyamine levels, mechanisms demonstrated by other cytotoxic polyamine analogues.

Synthesis of bis-spermine dimers that are potent polyamine transport inhibitors.

A series of novel spermine dimer analogues was synthesized and assessed for their ability to inhibit spermidine transport into MDA-MB-231 breast carcinoma cells. Two spermine molecules were tethered via their N(1) primary amines with naphthalenedisulfonic acid, adamantanedicarboxylic acid and a series of aliphatic dicarboxylic acids. The linked spermine analogues were potent polyamine transport inhibitors and inhibited cell growth cytostatically in combination with a polyamine synthesis inhibitor.