Effect of chitosan glutamate,carbomer 974P,and EDTA on the in vitro Caco-2 permeability and oral pharmacokinetic profile of acyclovir in rats

Background: Chitosan glutamate and polyacrylic acid (e.g., carbomer 974P) are known to modulate the tight junctions in the intestinal wall and increase permeability and blood exposure of drugs absorbed orally by the paracellular route. Aim: To assess the impact of chitosan glutamate and carbomer 974P on the absorption of paracellularly absorbed model drug, acyclovir, in vitro and in rat in vivo. Methods: The influence of chitosan glutamate and carbomer 974P (alone and in combination with EDTA–Na2) on the in vitro Caco-2 permeability and oral pharmacokinetic profile in the rat of acyclovir was investigated. Results: In the presence of chitosan glutamate, the apparent permeability of acyclovir across Caco2 monolayer increased 4.1 times relative to control. This increase was accompanied by a significant (～60%) decrease in transepithelial electrical resistance values indicating opening of the tight junctions in the cell monolayer. In rat, chitosan glutamate doubled oral bioavailability of acyclovir and tripled the amount of acyclovir excreted unchanged into urine. In contrast, the effect of carbomer 974P was not statistically significant at 5% level. Conclusions: In conclusion, chitosan glutamate (1–3%) and chitosan glutamate (1%)/EDTA–Na2 (0.01%) are effective excipients to increase permeability of acyclovir across Caco-2 cell monolayers and the oral absorption in the rat in vivo.     

Cell therapy using an array of ultrathin hollow microneedles

Microsystem Technologies - Cell transplantation traditionally employs needles to inject donor cells into tissues to treat certain diseases. However, it is difficult for the current method to...     

Development of Thermoelectric Self-Powered Heating Equipment

In this work, a self-powered residential heating system was developed using thermoelectric generation technology. A full-size prototype was designed, constructed, and tested, in which Bi₂Te₃-based thermoelectric modules were incorporated into a gas-fired heating boiler. Up to 161 W of electricity is generated by the thermoelectric modules. This is sufficient to power all the electrical components of the residential heating equipment including pump, fan, blower, valves, and control panel. In this way, the heating system can operate entirely on fuel combustion and does not need externally generated electricity. The performance of the thermoelectric devices has been investigated in the integrated heating system under various operating conditions. The energy system’s advantages include simplicity, low noise, clean operation, and low maintenance. The thermoelectric self-powered heating system could provide the consumer with heating system reliability and a reduction in electric power consumption.     

Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

The assembly of Ni2+-actin: some peculiarities

Cochlear implants have been very successful in restoring partial hearing to profoundly deaf people. Many individuals with implants are now able to communicate and understand speech without lip-reading, and some are able to talk over the phone. Children with implants can develop spoken-language skills and attend normal schools (i.e., schools with normal-hearing children). The greatest benefits with cochlear implantation have occurred in patients who (1) acquired speech and language before their hearing loss, and (2) have shorter duration of deafness. Gradual, but steady, improvements in speech production and speech perception have also occurred in prelingually deafened adults or children.     

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import

The Galbeta1-3GalNAcalpha (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 micrograms/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 micrograms/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.