Effect of pO2 and pH on synergy of tazobactam and β-lactam antibiotics against β-lactamase producing Enterobacteriaceae

Synergy between tazobactam and ceftriaxone or piperacillin against β-lactamase producing Enterobacteriaceae was not influenced by the presence or absence of oxygen. For most strains synergy was excellent at neutral pH but reduced in acidic conditions. Low pH increased 50% of the MICs up to or beyond the sensitivity breakpoin

"One face with tow sexes"? - Versuch, die Erkenntnisse aus einem psychophysikalischen Experiment zu deuten

One Face with Two Sexes?: Attempting to Analyze the Insights of a Psychophysical ExperimentThis article analyzes some very specific processes of knowledge and evidence production in the field of human psychophysics concerning the question of whether gender is a category of human visual perception, specifically of face recognition. Methodologically speaking, the article conducts a discursive analysis on a micro-political level and addresses the question of how the experiment itself and the form of knowledge behind it, together with the media devices employed, produce some kind of truth or evidence about gender as it is represented in the form of text, diagrams, and pictures. This kind of scientific “truth” was published in, Vision, one of the field’s preeminent scientific journals, in 2005. The media technique used in the experiment is a morphing procedure based on complicated statistical-mathematical calculations and elaborated algorithms. In terms of effect on the level of image production, the medium primarily erased all differences between two categories of sex, which were extracted from “reality” and then digitalized, but also an a priori presumption on the part of the experimenters. The following article shows how the morphing procedure destabilizes this presumption on an epistemological level; how the process of presenting the images to the subjects in a static, photographic manner seeks to regulate this destabilization; and how, finally, the presumption is – as experimental solution – at the risk of being unverifiable, but for this very reason has to be rationalized and reestablished in order to keep sexual difference intelligible in the form of two categories of sex

Monitoring serum concentrations for once-daily netilmicin dosing regimens

A once-daily dosing regimen for aminoglycosides is less expensive, at least as effective and possibly less toxic than multiple-daily dosing regimens. Once-daily dosing might also allow the frequency of measuring the serum concentrations of these antibiotics to be reduced since two of the major objectives of monitoring, high peak and low trough concentrations, are more likely to be achieved with this regimen. A novel strategy for monitoring serum concentrations which relies on a single sample obtained 8 h after a dose, as opposed to both trough and peak samples, is evaluated here. Serum kinetics of netilmicin were studied prospectively in 51 adult patients with initial serum creatinine concentrations of 25 μmol/L was detected in 0 of 7 patients with an 8-h concentration of 6 mg/L. The results of this study suggest that adequate information about serum netilmicin concentrations in patients receiving a once-daily dose may be derived from a sample obtained 8 h after administratio

Vitamin B12 as a carrier for targeted platinum delivery: in vitro cytotoxicity and mechanistic studies

It is attractive to use vitamin B12 as a carrier for targeted delivery of cytotoxic agents such as platinum complexes owing to the high demand for vitamin B12 by fast proliferating cells. The basic {B12-CN-PtII} conjugates are recognized by intracellular enzymes and converted to coenzyme B12 in an enzymatic adenosylation assay. The reductive adenosylation of {B12-CN-PtII} conjugates leads to the release of the PtII complexes; thus, {B12-CN-PtII} conjugates can be considered as prodrugs. It is important not only to elucidate the activity of the cisplatin-B12 conjugates, but also to understand the mode of action on a molecular level. Chemical reduction of {B12-CN-PtII} conjugates with cobaltocene yielded cob(II)alamin and induced release of the corresponding PtII species. Kurnakov tests and coordination of 2′-deoxyguanosine or GMP to the released PtII complexes allowed isolation and characterization of PtII complexes as released during enzymatic adenosylation. The biological activity of these PtII complexes was evaluated. Since the cleaved PtII complexes show cytotoxicity, the {B12-CN-PtII} conjugates can be used for specific targeting of cancer cells and therapeutic drug delivery. Preliminary in vitro cytotoxicity studies indicated lower activity (IC50 between 8 and 88μM) than found for pure cisplatin. Since active transport and receptor-mediated uptake limits the intracellular {B12-CN-PtII} concentration, comparison with pure cisplatin is of limited use. We could show that the PtII complexes cleaved from B12 exerted a cytotoxicity comparable to that of cisplatin itself. Cytotoxicity studies in vitamin B12 free media showed a dependence on the addition of transcobalamin II for B12-Pt(II) conjugate

Periodontal complications of hyperglycemia/diabetes mellitus: Epidemiologic complexity and clinical challenge

This report provides a comprehensive overview of the adverse effects of hyperglycemia on the periodontium. It combines data from literature reviews of original data from two large, population‐based epidemiologic studies with comprehensive periodontal health assessment. Emphasis is placed on the exploration of hitherto sparsely reported effects of prediabetes and poorly controlled (uncontrolled) diabetes, in contrast to the umbrella term “diabetes.” This stems from the realization that it is not simply having a diagnosis of diabetes that may adversely affect periodontal health. Rather, it is the level (severity) of hyperglycemia that is the determining factor, not the case definition of the diagnosis of diabetes or the type of diabetes in question. Importantly, based on existing evidence this paper also attempts to estimate the improvements in periodontal probing depth and clinical attachment level that can be expected upon successful nonsurgical periodontal treatment in people with chronic periodontitis, with and without diabetes, respectively. This exploration includes the implentation of new systematic reviews and meta‐analyses that allow comparison of such intervention outcomes between hyperglycemic and normoglycemic subjects. Based on both existing literature and original analyses of population‐based studies, we try to answer questions such as: Is there a glycated hemoglobin concentration threshold for periodontitis risk? Does short‐term periodontal probing depth reduction and clinical attachment level gain after scaling and root planing depend on glycemic control in type 2 diabetes? Are short‐term scaling and root planing outcomes in people with hyperglycemia/diabetes inferior to those in people without diabetes? Do periodontitis patients with diabetes benefit more from the use of adjuvant antibiotics with nonsurgical periodontal treatment than people without diabetes? Does hyperglycemia lead to greater tooth loss in patients in long‐term post‐periodontal treatment maintenance programs? Throughout this review, we compare our new findings with previous data and report whether the results of these new analyses corroborate, or are in discord with, similar scientific reports in the literature. We also explore the potential role of dental health‐care professionals in helping patients control the risk factors that are identical for periodontitis and diabetes. Finally, we suggest various topics that still need exploration in future research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146293/1/prd12235.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146293/2/prd12235_am.pd

Vergleich der systemischen Lyse und mechanischer Thrombektomie hinsichtlich des klinischen Behandlungserfolges von Patienten mit akutem thrombembolischen Schlaganfall

Ein Schlaganfall ist eine akut einsetzende zerebrale Minderperfusion des arteriellen Stromgebietes des Gehirns. Es kommt zu einer reversiblen oder irreversiblen Schädigung des Hirngewebes mit unterschiedlicher Ausprägung der geistigen und körperlichen Einschränkungen. Diesbezüglich wird in der folgenden Arbeit das Augenmerk auf das Outcome der Patienten hinsichtlich der Behandlungsoption mit einer systemischen Lyse oder mittels einer mechanischen Thrombektomie gelegt

Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS)

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct alcohol consumption markers widely used nowadays for clinical and forensic applications. They are detectable in blood and urine even after consumption of trace amounts of ethanol and for a longer time frame, being detectable even when no more ethanol is present. The instability of EtG against bacterial degradation in contaminated urine samples and/or the possible postcollection synthesis of this metabolite in samples containing, e.g., Escherichia coli and ethanol, may cause false identification of alcohol uptake. Therefore, it is of paramount importance to constrict these error sources by inhibition of any bacterial growth causing hydrolization or synthesis of EtG. This study evaluates a new method of collecting urine samples on filter paper, dried urine spots (DUS), for simultaneous detection of EtG, EtS and creatinine, having the great advantage of inhibiting bacterial activity. In addition, a method validation for the determination of EtG and EtS in DUS was performed according to the FDA guidelines. Sterile-filtered urine was spiked with EtG and EtS, inoculated with E. coli and incubated. Liquid and dried urine samples were collected after various time intervals up to 96h. Liquid samples were frozen immediately after collection, whereas aliquots for DUS were pipetted onto filter paper, allowed to dry and stored at RT until analysis 1week after. The specimens were analyzed by LC-ESI-MS/MS. As expected, degradation of EtG, but not of EtS, was observed in contaminated liquid urine samples. However, the specimens collected on filter paper and stored at RT showed no degradation during storage. Therefore, collecting urine samples on filter paper for EtG and EtS analysis turns out to be a reliable method to avoid bacterial degradation of EtG and EtS, and consequently, stabilization of these ethanol metabolites is achieved. In addition, simultaneous measurement of creatinine content as an indicator of urine dilution helps to interpret the results. Method validation for EtG and EtS in DUS was satisfactory, showing the linearity of the calibration curves in the studied concentration range, good precision, accuracy and selectivit

Processing of the Terminal Alpha-1,2-Linked Mannose Residues From Oligomannosidic N-Glycans Is Critical for Proper Root Growth

N-glycosylation is an essential protein modification that plays roles in many diverse biological processes including protein folding, quality control and protein interactions. Despite recent advances in characterization of the N-glycosylation and N-glycan processing machinery our understanding of N-glycosylation related processes in plant development is limited. In Arabidopsis thaliana, failure of mannose trimming from oligomannosidic N-glycans in the endoplasmic reticulum (ER) and cis/medial-Golgi leads to a defect in root development in the mns123 triple mutant. Here, we show that the severe root phenotype of mns123 is restored in asparagine-linked glycosylation (ALG)-deficient plants with distinct defects in the biosynthesis of the lipid-linked oligosaccharide precursor. The root growth of these ALG-deficient plants is not affected by the α-mannosidase inhibitor kifunensine. Genetic evidence shows that the defect is uncoupled from the glycan-dependent ER-associated degradation (ERAD) pathway that removes misfolded glycoproteins with oligomannosidic N-glycans from the ER. Restoration of mannose trimming using a trans-Golgi targeted α-mannosidase suppresses the defect of mns123 roots. These data suggest that processing of terminal mannose residues from oligomannosidic N-glycans is important for an unknown late-Golgi or post-Golgi process that is implicated in proper root formation