Development of a valve type semi-closed extracorporeal circulation system.

In Japan, perfusionists who work on other clinical tasks are involved in cardiopulmonary bypass. Moreover, the number of cases they can perform is limited. In view of this situation, valve type semi-closed extracorporeal circulation (VACC) was developed as a system that enables extracorporeal circulation (ECC) regardless of perfusionists' experience. The VACC circuit is based on a conventional open-type ECC circuit. A safety valve is installed at the outlet of the reservoir. It is closed by lowering the reservoir pressure below the venous circuit pressure (Pv), thereby providing a closed-type ECC in which the reservoir is separated from the venous circuit (V-circuit). A closed-type ECC needs means to cope with negative pressure generated in the V-circuit and to remove air mixed in the V-circuit. Water experiments to verify the safety of the VACC were conducted. In experiments simulating low venous return, when the Pv dropped, the safety valve opened so that the V-circuit was connected to the reservoir, and the excessive negative pressure was relieved. In the VACC circuit, a bubble trap is installed in the V-circuit, and the air is degassed to the reservoir by a roller pump (D-pump). A water experiment was conducted to verify the principle of the constant degassing method using the D-pump. It verified that the blood storage volume could be maintained constant even if the D-pump is continuously driven. The VACC system provides handling of air mixed in the V-circuit and safety in the case of low venous return.

Combination Strategy with Complexation Hydrogels and Cell-Penetrating Peptides for Oral Delivery of Insulin.

In previous studies we showed that the complexation hydrogels based in poly(methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)] rapidly release insulin in the intestine owing to their pH-dependent complexation properties; they also exhibit a high insulin-loading efficiency, enzyme-inhibiting properties, and mucoadhesive characteristics. Cell-penetrating peptides (CPPs), such as oligoarginines [hexa-arginine (R6), comprising six arginine residues], have been employed as useful tools for the oral delivery of therapeutic macromolecules. The aim of our study was to investigate the combination strategy of using P(MAA-g-EG) hydrogels with R6-based CPPs to improve the intestinal absorption of insulin. A high efficiency of loading into crosslinked P(MAA-g-EG) hydrogels was observed for insulin (96.1±1.4%) and R6 (46.6±3.8%). In addition, immediate release of the loaded insulin and R6 from these hydrogels was observed at pH 7.4 (80% was released in approximately 30 min). Consequently, a strong hypoglycemic response was observed (approximately 18% reduction in blood glucose levels) accompanied by an improvement in insulin absorption after the co-administration of insulin-loaded particles (ILP) and R6-loaded particles (ALP) into closed rat ileal segments compared with that after ILP administration alone. These results indicate that the combination of P(MAA-g-EG) hydrogels with CPPs may be a promising strategy for the oral delivery of various insulin preparations as an alternative to conventional parenteral routes.

Are individuals with lower neutrophil oxidative burst activity more prone to Helicobacter pylori infection?

Helicobacter pylori infection has been reported to cause enhanced reactive oxygen species in the gastric mucosa. We examined the relationship between H. pylori infection and neutrophil function of peripheral blood. The subjects were 904 volunteers who participated in the Iwaki Health Promotion Project in 2005. 158 subjects who were infected with H. pylori in 2005 also participated in this project in 2006 and were categorized into two groups: the eradication group, in which H. pylori was successfully eradicated during the 12 month period, and the non-eradication group, in which eradication was unsuccessful or the subjects did not receive eradication therapy. The laboratory assays performed were: a titre of H. pylori antibody; neutrophil counts; and oxidative burst activity (OBA) of neutrophils. Logistic regression analysis was executed, with H. pylori infection as the dependent variable and other items as the independent variables. OBA showed an inverse association with H. pylori infection in 2005. Additionally, when comparing the eradication and non-eradication groups, the change rates of OBA between 2005 and 2006 did not show any significant difference. It was concluded that H. pylori infection does not lower OBA, but those individuals in whom OBA was lower were more prone to H. pylori infection.

Characterization of insulin protection properties of complexation hydrogels in gastric and intestinal enzyme fluids.

The objective of this study was to elucidate the mechanisms contributing to oral bioavailability of insulin by poly(methacrylic acid grafted with poly(ethylene glycol)) (P(MAA-g-EG)) hydrogels using the gastric and intestinal fluids from rats. P(MAA-g-EG) hydrogels successfully protected the incorporated insulin from enzymatic degradation by forming interpolymer complexes in the gastric fluid. The hydrogels also showed the insulin protection ability by itself. In the intestinal fluid, P(MAA-g-EG) hydrogels significantly decreased the insulin degradation rate and calcium ion levels, while protein levels was not changed. Insulin protecting effects were dependent on the fraction of the carboxylic group in the polymer networks. Moreover, the insulin degradation inhibitory effect was significantly correlated with Ca2+ deprivation ability of P(MAA-g-EG) hydrogels in the intestinal fluid, implying that the Ca2+ deprivation ability plays an important role in the inhibition of the intestinal enzyme activities. Insulin-loaded P(MAA-g-EG) (ILPs) hydrogels showed a rapid and almost complete insulin release even in the presence of intestinal proteases. These results suggested that the insulin protection ability of the hydrogels contributed to improve oral insulin absorption and that P(MAA-g-EG) hydrogels can be an excellent carrier for protecting insulin during their transit through the GI tract.