Peptide/β-Peptoid Hybrids with Activity against Vancomycin-Resistant Enterococci: Influence of Hydrophobicity and Structural Features on Antibacterial and Hemolytic Properties

Infections with enterococci are challenging to treat due to intrinsic resistance to several antibiotics. Especially vancomycin-resistant Enterococcus faecium and Enterococcus faecalis are of considerable concern with a limited number of efficacious therapeutics available. From an initial screening of 20 peptidomimetics, 11 stable peptide/β-peptoid hybrids were found to have antibacterial activity against eight E. faecium and E. faecalis isolates. Microbiological characterization comprised determination of minimal inhibitory concentrations (MICs), probing of synergy with antibiotics in a checkerboard assay, time–kill studies, as well as assessment of membrane integrity. E. faecium isolates proved more susceptible than E. faecalis isolates, and no differences in susceptibility between the vancomycin-resistant (VRE) and -susceptible E. faecium isolates were observed. A test of three peptidomimetics (Ac-[hArg-βNsce]₆-NH₂, Ac-[hArg-βNsce-Lys-βNspe]₃-NH₂ and Oct-[Lys-βNspe]₆-NH₂) in combination with conventional antibiotics (vancomycin, gentamicin, ciprofloxacin, linezolid, rifampicin or azithromycin) revealed no synergy. The same three potent analogues were found to have a bactericidal effect with a membrane-disruptive mode of action. Peptidomimetics Ac-[hArg-βNsce-Lys-βNspe]₃-NH₂ and Oct-[Lys-βNspe]₆-NH₂ with low MIC values (in the ranges 2–8 µg/mL and 4–16 µg/mL against E. faecium and E. faecalis, respectively) and displaying weak cytotoxic properties (i.e., <10% hemolysis at a ~100-fold higher concentration than their MICs; IC₅₀ values of 73 and 41 µg/mL, respectively, against HepG2 cells) were identified as promising starting points for further optimization studies.     

Not so ugly after all: When shame acts as a commitment device.

Most psychological theories and research on shame focus on the ugly aspects and negative consequences of this emotion. Theories on moral emotions, however, assume that shame acts as a commitment device motivating prosocial behavior. To solve this apparent paradox, the authors studied the effects of shame on prosocial behavior. Shame was hypothesized to motivate prosocial behavior when it was relevant for the decision at hand (endogenous). In contrast, shame that was not relevant for the decision at hand (exogenous) was hypothesized to have no such effects. Four experiments with three different shame inductions and two different measures of prosocial behavior confirmed that endogenous shame motivated prosocial behavior for proselfs but that exogenous shame did not. Shame is shown to have a clear interpersonal function in the sense that it acts as a commitment device. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Removal of neutrophil gelatinase‐associated lipocalin by extracorporeal therapies

Neutrophil gelatinase‐associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30‐minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 μg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 μg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.     

Permanent open shunt as a reason for impotence or reduced potency after surgical treatment of priapism in 26 patients

A permanent open shunt as a cause of impotence or impaired potency after a shunt operation for priapism is an unusual situation. In this series we studied the persistence of an open shunt in 26 patients who had developed impotence or impaired potency after operative treatment for priapism. All patients had been examined by cavernosography on the suspicion of an open shunt, giving a positive finding in five of 26 cases, in all of which impotence was cured by closure of the shunt. In five patients without a permanent open shunt potency returned to normal only after 6-12 months.     

Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer

The aim of this prospective study was to investigate if high uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) is associated with aggressiveness in head and neck cancer and low probability of survival. METHODS: Thirty-seven patients with squamous-cell carcinoma of the head and neck underwent FDG-PET in the fasting state before cancer treatment. FDG uptake in primary tumor was quantitated as the standardized uptake value of FDG normalized to the predicted lean body mass (SUVlean, n = 37) and as the graphically determined metabolic rate for FDG (rMR[FDG], n = 34). Paraffin-embedded tumor samples were used for histologic evaluation, and expression of cytokeratin and Ki-67 antigen were assessed by immunohistochemistry. RESULTS: Interobserver agreement for the determination of quantitative uptake of FDG in tumors was excellent (r2 = 0.996, p < 0.00001), and all 37 primary tumors were visualized. A high uptake of FDG as assessed by SUVlean was associated with a higher than the median mitotic count (p = 0.01), absence of keratinization (p = 0.03), low or moderate histological grade of differentiation (p = 0.046) and advanced stage (p = 0.03), but not with Ki-67 expression (p = 0.11). The overall survival of patients with a SUVlean lower than or equal to the median value (9.0) was clearly better in univariate analysis than that of patients with a SUVlean higher than the median (3-yr survival 73% versus 22%, relative risk of death (RR) 4.2, 1.6-11.0). However, in a multivariate analysis the only independent predictors of survival were the mitotic count (RR 4.0, 1.4-11.7) and stage (3.8, 1.2-12.2). CONCLUSION: High uptake of FDG in untreated head and neck cancer is associated with advanced disease, and may portend poor survival. Aggressive treatment approaches should be considered for patients presenting with a tumor with high uptake of FDG.     

Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal dialysis

BACKGROUND: The surface-active substance dioctyl sodium sulphosuccinate (DSS) has been reported to increase the peritoneal clearances of urea and creatinine. This study investigated the effects of DSS on the fluid and solute transport characteristics of the peritoneum. DESIGN: A 4-h single-dwell experiment session of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was given to the other eight rats (control group). The transport of fluid, glucose, potassium, sodium, urea, phosphate and urate were analysed. RESULTS: There was a significant increase in the intraperitoneal volume in the DSS group. At 240 min, the drain volume in DSS group (33.0 +/- 2.9 ml) was significantly higher compared to the control group (28.8 +/- 2.1 ml, P < 0.01). This increase in the drain volume was mainly due to a decrease in peritoneal fluid absorption rate in the DSS group (0.040 +/- 0.013 ml/min) as compared to the control group (0.054 +/- 0.010 ml/min, P < 0.05). There was no significant difference in the diffusive permeability and sieving coefficient for the small solutes between these two groups. However, the clearances for urea and sodium were higher in the DSS group, mainly due to the increase in the dialysate volume. CONCLUSION: Our results suggest that DSS significantly increases the net ultrafiltration of peritoneal dialysis. This effect, which was mainly due to a decrease in the fluid absorption rate, contributed to the increased clearances for urea and sodium. DSS did not alter the diffusive permeability and sieving coefficient for the small solutes.     

Relearning face-name associations in early Alzheimer's disease.

Preliminary evidence for the effectiveness of cognitive rehabilitation interventions based on errorless learning principles in early-stage Alzheimer's disease (AD) was provided by Clare et al. (1999, 2000, 2001). The present study extends these findings in a controlled trial. Twelve participants meeting criteria for probable AD, with Mini-Mental State Examination scores of 18 or above, were trained in face-name associations using an effortless learning paradigm. Training produced a significant group improvement in recall of trained, but not control, items. Gains were largely maintained 6 months later, in the absence of practice. There were differences in individual response to intervention. Results did not differ according to medication status, and the intervention had no adverse effects on self-reported well-being, but participants who were more aware of their memory difficulties achieved better outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bioactive double glass coatings for Co-Cr-Mo alloy

Glass compositions for double coatings for a Co-Cr-Mo alloy were developed. The glass compositions were chosen to fulfil such requirements as matching thermal expansion, low glass transition temperature and moderate solubility. For the ground coat a fairly high durability is required, whereas the cover coat must be bioactive, i.e. become attached to living bone by a chemical bond. Two compositions of each type were developed by computer-aided optimization. The glasses were chosen in the Na₂O–CaO–B₂O₃–Al₂O₃–SiO₂–P₂O₅ system. The bioactivity was tested in vitro by immersion in a simulated body fluid. The double coatings on Co–Cr–Mo alloy released hexavalent chromium into the solution as detected by yellow colouration and spectrophotometry. This colouration was strong at the margin between coated and uncoated metal and may be explained by oxidation of trivalent chromium of the alloy in the presence of glass. The released chromium did not have any notable effect on the calcium phosphate formation. After replensihing the solution no coloration was observed. This suggests that the chromate is easily dissolved and that it may be possible to wash it out prior to implantation.     

Experimental telemedicine in orthopaedics

An accurate technique that simplifies measurements of two- and three-dimensional specimens is presented. Photomicrographs of a microruler and of the specimens of a research project were made at the same magnification. A ruler with the exact dimensions of the photographic prints of the microruler was generated through computer graphics and printed as a transparency. After verification, the ruler was used to measure specimens directly on the photomicrographs.