Quercetin mediated antimicrobial photodynamic treatment using blue light on Escherichia coli O157:H7 and Listeria monocytogenes.

Interest in using an antimicrobial photodynamic treatment (aPDT) for the microbial decontamination of food has been growing. In this study, quercetin, a substance found ubiquitously in plants, was used as a novel exogenous photosensitizer with 405 nm blue light (BL) for the aPDT on foodborne pathogens, and the inactivation mechanism was elucidated. The inactivation of Escherichia coli O157:H7 and Listeria monocytogenes in PBS solution by the quercetin and BL combination treatment reached a log reduction of 6.2 and more than 7.55 at 80 J/cm2 (68 min 21 s), respectively. When EDTA was added to investigate the reason for different resistance between two bacteria, the effect of aPDT was enhanced against E. coli O157:H7 but not L. monocytogenes. This result indicated that the lipopolysaccharide of Gram-negative bacteria operated as a protective barrier. It was experimentally demonstrated that quercetin generated the superoxide anion and hydrogen peroxide as the reactive oxygen species that oxidize and inactivate cell components. The damage to the bacterial cell membrane by aPDT was evaluated by propidium iodide, where the membrane integrity significantly (P < 0.05) decreased from 40 J/cm2 compared to control. In addition, DNA integrity of bacteria was significantly (P < 0.05) more decreased after aPDT than BL treatment. The inactivation results could be applied in liquid food industries for decontamination of foodborne pathogens, and the mechanisms data was potentially utilized for further studies about aPDT using quercetin.

Small-molecule drug screening identifies drug Ro 31-8220 that reduces toxic phosphorylated tau in Drosophila melanogaster.

The intraneuronal aggregates of hyperphosphorylated and misfolded tau (neurofibrillary tangles, NFTs) cause a stereotypical spatiotemporal Alzheimer's disease (AD) progression that correlates with the severity of the associated cognitive decline. Kinase activity contributes to the balance between neuron survival and cell death. Hyperactivation of kinases including the conventional protein kinase C (PKC) is a defective molecular event accompanying associative memory loss, tau phosphorylation, and progression of AD or related neurodegenerative diseases. Here, we investigated the ability of small therapeutic compounds (a custom library) to improve tau-induced rough-eye phenotype in a Drosophila melanogaster model of frontotemporal dementia. We also assessed the tau phosphorylation in vivo and selected hit compounds. Among the potential hits, we investigated Ro 31-8220, described earlier as a potent PKCα inhibitor. Ro 31-8220 robustly improved the rough-eye phenotype, reduced phosphorylated tau species in vitro and in vivo, reversed tau-induced memory impairment, and improved the fly motor functions. In a human neuroblastoma cell line, Ro 31-8220 reduced the PKC activity and the tau phosphorylation pattern, but we also have to acknowledge the compound's wide range of biological activity. Nevertheless, Ro 31-8220 is a novel therapeutic mitigator of tau-induced neurotoxocity.

Uncaria rhynchophylla ameliorates amyloid beta deposition and amyloid beta-mediated pathology in 5XFAD mice.

One of the pathological hallmarks of Alzheimer's disease (AD) is the abnormal aggregation of amyloid beta (Aß) peptides. Uncaria rhynchophylla (UR), one of the Uncaria species, has long been used to treat neurodegenerative disease. In particular, it has been reported that UR inhibits aggregation of Aß in vitro. However, little is known about the histological effects of UR treatment on Aß pathology in AD animal models. In the present study, we investigated the effect of UR on Aß aggregation, Aß-mediated pathologies and adult hippocampal neurogenesis in the brain of 5XFAD mice. First, using the thioflavin T assay and amyloid staining, we demonstrated that UR treatment effectively inhibited Aß aggregation and accumulation in the cortex and subiculum. Second, immunofluorescence staining showed that administration of UR attenuated gliosis and neurodegeneration in the subiculum and cortex. Third, UR treatment ameliorated impaired adult hippocampal neurogenesis. The present results indicate that UR significantly alleviates Aß deposition and Aß-mediated neuropathology in the brain in 5XFAD mice, suggesting the potency of UR as a preventive and therapeutic agent for AD.

Intralipid Restoration of Myocardial Contractions Following Bupivacaine-Induced Asystole: Concentration- and Time-Dependence In Vitro.

BACKGROUND: The concentration- and time-response relationships of lipid emulsion (LE; Intralipid) on the recovery of myocardial contractility following bupivacaine (BPV)-induced asystole are poorly defined. METHODS: After achieving asystole by 500-µM BPV, varied concentrations of LE were applied to determine the recovery of stimulated contractile responses and contractions in the cardiac tissues of guinea pigs at a 1.2-Hz stimulation rate. These experiments were performed with LE in either a recirculating (2%-16%) or washout (nonrecirculating) condition (0.05%-12%) for 60 minutes. The effect of LE itself (0.05%-12%) was examined. Oxfenicine was used to evaluate the metabolic action of LE to reverse asystole. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculation condition, partial recovery of contractile forces was observed for 60 minutes at 4%, 8%, and 12% LE. A contracture followed after exposure to 16% LE in some asystolic muscles. In the washout experiments, following asystole, LE (0.05%-12%) had no effect on the recovery time of the first and regular contractile responses. LE (0.1%-8%) restored contractility to baseline levels after 45 minutes; partial recovery was shown with lower (0.05%) and higher (12%) concentrations. Oxfenicine did not alter the recovery of contractile forces. Contractile depression was observed with 12% LE alone. Concentration-related reduction of tissue BPV concentration by LE was observed in both circulating conditions. CONCLUSIONS: LE induced time- and concentration-dependent recovery of stimulated myocardial contractions from BPV-induced asystole. The lipid uptake effect, along with other undefined mechanisms of LE, seems to contribute to the recovery of contractile function; however, the LE effect on myocardial metabolism is less likely involved at this concentration (500 µM) of BPV.

Clinical use of alumina-toughened zirconia abutments for implant-supported restoration: prospective cohort study of survival analysis.

OBJECTIVES: The aim of this prospective cohort study was to compute the long-term clinical survival and complication rates of alumina-toughened zirconia abutments used for implant-supported restorations and to evaluate the effects of several clinical variables on these rates. MATERIAL AND METHODS: From May 1998 to September 2010, 213 patients aged 18 years or older were recruited. The patients received 611 external hex implants and 328 implant-supported fixed restorations using alumina-toughened zirconia abutments. During the follow-up, each restoration was coded as a dental event, which included loosening or fracture of abutment screws, and abutment fracture. From the coded data, the effects of the investigated clinical variables-restored area (anterior/posterior), number of prosthodontic units (one/two units or over), prosthesis type (single-unit/multiunit without pontic/multiunit with pontic), implant system, and patient gender-on the survival of the abutments were evaluated. Survival analysis using Kaplan-Meier method and Cox proportional hazard model was applied. The 5-year survival and complication rates of the abutments were assessed. RESULTS: The number of prosthodontic units and the type of prosthesis had a significant association with complication rates (P < 0.05). Kaplan-Meier survival analysis estimated that the cumulative 5-year complication rate of the abutments used in single restorations was 19.7%. Multiunit-fixed dental prostheses without and with pontics had complication rates of 3.9% and 3.8%, respectively. The 5-year survival rate of the abutments was more than 95%, regardless of the type of prosthesis. CONCLUSIONS: Alumina-toughened zirconia abutments are likely to exhibit excellent long-term survival in clinical use for fixed restorations. Single tooth replacement with the abutment at the molar region may require special care and extra attention.

Combined anti-calcification treatment of bovine pericardium with amino compounds and solvents.

The objective of this study was to evaluate the effect of treatment with amino compounds and solvents in vivo on calcifications of glutaraldehyde (GA)-fixed pericardium. Groups of bovine pericardium samples were fixed with 0.5% GA. We used urazole and glutamate to neutralize the free aldehyde and some solvents (ethanol with octanol or octanediol) to reduce the phospholipid content in the bovine pericardial tissue. Tensile strength and thermal stability were evaluated before implantation. Twelve weeks after rat subdermal implantation, the pericardial samples were harvested from eight juvenile rats. Urazole [calcium (Ca(2+)): 11.86 ± 2.85 µg/mg; inorganic phosphorus (IP): 32.59 ± 7.73 µg/mg] or glutamate (Ca(2+): 7.95 ± 1.21 µg/mg; IP: 21.76 ± 3.48 µg/mg) alone significantly decreased the Ca(2+) and IP concentrations (without any anti-calcification treatment, Ca(2+): 277.85 ± 17.51 µg/mg; IP: 147.07 ± 8.32 µg/mg), but when used with organic solvents, the Ca(2+) and IP concentrations were the lowest (Ca(2+): 0.05 ± 0.04 µg/mg; IP: 3.36 ± 0.61 µg/mg). After anti-calcification treatment, the calcifications in microscopic images were dramatically decreased. Anti-calcification treatment with glutamate, urazole, and solvents did not worsen the physical properties of bovine pericardium, and significantly prevented in vivo calcifications compared to GA fixation only. There should be additional studies done to understand the other mechanism underlying xenograft tissue calcification.

Protective effects of cranberries on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux.

OBJECTIVE: To evaluate the protective effects of cranberry fruit, which have known antioxidant effects, on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux (VUR). MATERIALS AND METHODS: In all, 36 New Zealand male rabbits were divided into five groups, with a sham operation in four rabbits serving as the control (group 1). To create unilateral VUR the roof of the left intravesical ureter was incised, and VUR confirmed 2 weeks after surgery. In all, 32 rabbits with VUR were divided into four groups; 2, VUR alone (with sterile urine); 3, a group infected with Escherichia coli; 4, with intravesical E. coli instillation but fed cranberries; and 5, intravesical E. coli instillation plus an intraperitoneal injection with melatonin group. At 3 weeks after surgery the rabbits were killed, the kidneys obtained and examined histopathologically to evaluate inflammation, fibrosis and tubular changes. Oxidative renal damage was evaluated by measuring malondialdehyde in the renal tissue. RESULTS: Grossly, the refluxing kidney was larger than the contralateral normal kidney, and the refluxing ureter was dilated and tortuous. Microscopy of tissues from the kidneys in group 3 showed apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from groups 2, 4 and 5 showed mild mononuclear cell infiltration with no interstitial fibrosis. The level of malondialdehyde in the kidneys of group 3 was significantly higher than that in group 2, 4 and 5 (P < 0.05); the level in groups 4 and 5 did not differ significantly from that in group 2. CONCLUSIONS: This study shows that cranberries have an anti-inflammatory effect through their antioxidant function and might prevent infection-induced oxidative renal damage. Thus, clinically cranberries might be used as a beneficial adjuvant treatment to prevent damage due to pyelonephritis in children with VUR.

Subcellular localization of MURA and MURB proteins encoded by the maize MuDR transposon.

MuDR controls transposition of the Mu transposable element family in Zea mays L. It produces two major transcripts: mudrA and mudrB, mudrA encodes the MURA transposase, but no specific function has been ascribed to mudrB, which lacks strong homology to known genes. Using transient expression assays in onion epidermal cells, we defined three monopartite nuclear localization signals (NLSs) of MURA; each was functionally sufficient for nuclear targeting of MURA:GUS fusion proteins. Interestingly, one NLS (NLS-A3) is produced by the splicing of the third intron. In contrast, there were no clear NLS in MURB, and the major form of MURB aggregated in the cytoplasm. Self-interaction of MURA and of MURB was also shown in a yeast two-hybrid assay. To test whether interactions of MURA and MURB can occur at the level of protein translocation into the nucleus, a cytoplasmically localized MURB:GFP was co-expressed with MURA or with the GUS fusion proteins. Co-expression did not change the localization pattern of either MURA or MURB; MURA and MURB do not detectably interact in a yeast two-hybrid assay. These results suggest that MURA and MURB do not mutually affect their localization, at least in the forms examined here.