The success of the Edmonton Protocol for islet transplantation has provided new hope in the treatment of type 1 diabetes. This study reports on the assessment of 83 human islet grafts transplanted using the Edmonton Protocol since 1999. Cellular composition, as assessed by immunohistochemistry, showed a lower islet purity (ϳ40%) than has been reported in previous studies using dithizone staining to quantitate islet equivalents. Furthermore, grafts were found to contain substantial populations of exocrine and ductal tissue. Total cellular insulin transplanted was 8,097.6 ؎ 3,164.4 g/patient, and was significantly lower in bottom gradient layer grafts than top gradient layer or whole/combined grafts (P < 0.0005). A static incubation test for islet function gave a stimulation index of 3-4, although this measure did not correlate with posttransplant metabolic outcome. Furthermore, we confirmed a previously reported trend in which donor age affects islet yield and purity. It is important to note that a significant positive correlation was observed between the number of islet progenitor (ductal-epithelial) cells transplanted and long-term metabolic success as assessed an by intravenous glucose tolerance test at ϳ2 years posttransplant. In summary, careful assessment of islet graft composition is needed in a clinical transplantation program to accurately estimate islet purity and assess the contribution of other cell types present, such as islet progenitor cells.
BackgroundThe widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models.ResultsFollowing irradiation of wounds with 360 J/cm2 of laser light (670 nm) in the presence of 100 μg/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours.ConclusionThe results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites.
Covalently coupling toluidine blue O-tiopronin to a gold nanoparticle forms an enhanced, exceptionally potent antimicrobial agent when activated by white light or 632 nm laser light. Aqueous solutions of tiopronin-gold nanoparticles had no antimicrobial effect and, when added to solutions of toluidine blue O, did not enhance the antimicrobial effect of the latter. The minimum bactericidal concentration of the covalently coupled toluidine blue O-tiopronin gold conjugate for Staphylococcus aureus was at least four times lower than that of free toluidine blue O.
aPDT treatment may augment periodontal treatment by increasing bacterial killing, inactivating bacterial virulence factors, and inactivating host cytokines that impair periodontal restoration. Therefore, aPDT treatment may provide a more favorable healing environment.
This study demonstrated that three important periopathogens are susceptible to aPDT-mediated killing, regardless of whether they are present in planktonic or biofilm form. Furthermore, a clear energy dose-dependence exists with this treatment that should to be taken into account when determining optimal treatment times in clinical application.
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