Pharmaceutical Properties of a Tinted Formulation of a Biguanide Antiseptic Agent, Olanexidine Gluconate.

Olanexidine gluconate-containing preoperative antiseptic (OLG-C) is colorless, which makes it difficult to determine its area of application. To overcome this drawback, we realized a stable orange-tinted antiseptic (OLG-T) by adding new additives to OLG-C and investigated its pharmaceutical properties compared with OLG-C and povidone iodine (PVP-I). We evaluated the influence of the additives on the antimicrobial activity and adhesiveness of medical adhesives to OLG-T-applied skin by in vitro time-kill/ex vivo micropig skin assays and a peel test using excised micropig skin, respectively. In the in vitro time-kill assay, the bactericidal/fungicidal activity of OLG-T and OLG-C were equivalent. In the ex vivo micropig skin assay, their fast-acting and persistent bactericidal activities against vancomycin-resistant Enterococcus faecalis were higher than that of PVP-I. In the peel test, the adhesion force of the incise drape and the amount of stripped corneocytes on the peeled drape were comparable between OLG-T- and OLG-C-applied skin, but both were less than those of PVP-I-applied skin. The drapes for OLG-T- and OLG-C-applied skin had moderate adhesion force, and the drape-related injuries were expected to be weak. These results suggest that OLG-T performs no worse than OLG-C in terms of its antimicrobial activity and medical adhesive compatibility. Therefore, we expect OLG-T to lead to more convenient preoperative skin preparation and further contribute to lowering surgical site infection rates.

Evaluation of in Vitro Bactericidal Activity of 1.5% Olanexidine Gluconate, a Novel Biguanide Antiseptic Agent.

Recently, 1.5% olanexidine gluconate, a biguanide compounds, was launched as a new antiseptic agent in Japan. However, the comprehensive bactericidal spectrum of olanexidine gluconate is still unknown. In this study, we evaluated in vitro bactericidal activity of olanexidine gluconate using time-kill assay against various bacteria, mycobacteria, and fungi. With the exception of Burkholderia cepacia and Mycobacterium spp., 1.5% olanexidine gluconate exhibited fast-acting (≤60 s) bactericidal activity against all tested Gram-positive and Gram-negative bacteria, including vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, extended spectrum ß-lactamase producing Klebsiella pneumoniae, and multidrug-resistant Pseudomonas aeruginosa. Furthermore, 1.5% olanexidine gluconate eradicated Candida albicans, Microsporum canis, and Malassezia furfur within 3 min. Our findings indicate that olanexidine gluconate has broad spectrum bactericidal activity; therefore, it may be useful for the prevention of a wide range of infectious diseases.

Evaluation of fast-acting bactericidal activity and substantivity of an antiseptic agent, olanexidine gluconate, using an ex vivo skin model.

PURPOSE: We assessed the fast-acting bactericidal activity and substantivity of olanexidine gluconate (OLG) to investigate its remaining bactericidal activity on the skin after rinsing and drying by using an ex vivo Yucatan micropig (YMP) skin model. METHODOLOGY: The fast-acting bactericidal activity was evaluated in pigskin models inoculated with methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, vancomycin-resistant Enterococcus faecalis (VRE), Acinetobacter baumannii, Corynebacterium minutissimum and Cutibacterium acnes. To evaluate substantivity, the YMP skin piece first had 1.5 % OLG, chlorhexidine gluconate (CHG) formulations or 10 % povidone-iodine (PVP-I) applied to it, and was then rinsed with distilled water, incubated for 4, 6, 8 or 12 h and inoculated with the test bacteria (MRSA, S. epidermidis and VRE). The viable bacteria remaining at 1 min of exposure of bacteria were counted to measure the quantity of antiseptic molecules retaining bactericidal activity. To determine the factors contributing to the substantivity, the stratum corneum (SC) of the YMP skin that had had OLG or CHG applied to it was exfoliated using a tape-stripping method and the amount of antiseptic was quantitated. RESULTS: OLG showed a fast-acting bactericidal activity that was similar to or stronger than that of CHG formulations up to a concentration of 1 % and PVP-I with a short exposure time of 30 s, and substantivity until 12 h after rinsing, whereas the other antiseptics hardly showed any substantivity. There was 2.8 times or more OLG in the SC than CHG. CONCLUSION: OLG has fast-acting activity and substantivity, which are required properties for an antiseptic, and is useful for preventing infections.

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models.

Alzheimer's disease (AD) is the most common form of dementia. Cellular AD models derived from human pluripotent stem cells are promising tools in AD research. We recently developed human embryonic stem cell-derived AD models which overexpress mutant Presenilin1 genes, and which exhibit AD phenotypes, including synaptic dysfunction. In this study, we found that our AD models showed reduced levels of RAB3A and SV2B proteins in the pre-synapses, which is a possible cause of electrophysiological abnormalities. Through the screening of chemical compounds using our AD models, we have identified Aß peptide inhibitors which decrease the concentration of Aß in culture supernatant. Among these, BMS-708163 and Nilotinib were found to improve the expression levels of RAB3A and SV2B proteins and to recover the electrophysiological function in our AD models. These results suggest that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function.

The modeling of Alzheimer's disease by the overexpression of mutant Presenilin 1 in human embryonic stem cells.

Cellular disease models are useful tools for Alzheimer's disease (AD) research. Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), are promising materials for creating cellular models of such diseases. In the present study, we established cellular models of AD in hESCs that overexpressed the mutant Presenilin 1 (PS1) gene with the use of a site-specific gene integration system. The overexpression of PS1 did not affect the undifferentiated status or the neural differentiation ability of the hESCs. We found increases in the ratios of amyloid-ß 42 (Aß42)/Aß40 and Aß43/Aß40. Furthermore, synaptic dysfunction was observed in a cellular model of AD that overexpressed mutant PS1. These results suggest that the AD phenotypes, in particular, the electrophysiological abnormality of the synapses in our AD models might be useful for AD research and drug discovery.