High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics

Thirty-fold: Extreme gravitational lensing of a quiescent galaxy at z=1.6z=1.6

We report the discovery of eMACSJ1341-QG-1, a quiescent galaxy at $z=1.594$ located behind the massive galaxy cluster eMACSJ1341.9$-$2442 ($z=0.835$). The system was identified as a gravitationally lensed triple image in Hubble Space Telescope images obtained as part of a snapshot survey of the most X-ray luminous galaxy clusters at $z>0.5$ and spectroscopically confirmed in ground-based follow-up observations with the ESO/X-Shooter spectrograph. From the constraints provided by the triple image, we derive a first, crude model of the mass distribution of the cluster lens, which predicts a gravitational amplification of a factor of $\sim$30 for the primary image and a factor of $\sim$6 for the remaining two images of the source, making eMACSJ1341-QG-1 by far the most strongly amplified quiescent galaxy discovered to date. Our discovery underlines the power of SNAPshot observations of massive, X-ray selected galaxy clusters for lensing-assisted studies of faint background populations

Probabilistic Search for Object Segmentation and Recognition

The problem of searching for a model-based scene interpretation is analyzed within a probabilistic framework. Object models are formulated as generative models for range data of the scene. A new statistical criterion, the truncated object probability, is introduced to infer an optimal sequence of object hypotheses to be evaluated for their match to the data. The truncated probability is partly determined by prior knowledge of the objects and partly learned from data. Some experiments on sequence quality and object segmentation and recognition from stereo data are presented. The article recovers classic concepts from object recognition (grouping, geometric hashing, alignment) from the probabilistic perspective and adds insight into the optimal ordering of object hypotheses for evaluation. Moreover, it introduces point-relation densities, a key component of the truncated probability, as statistical models of local surface shape.Comment: 18 pages, 5 figure

Quantum chaos in nanoelectromechanical systems

We present a theoretical study of the electron-phonon coupling in suspended nanoelectromechanical systems (NEMS) and investigate the resulting quantum chaotic behavior. The phonons are associated with the vibrational modes of a suspended rectangular dielectric plate, with free or clamped boundary conditions, whereas the electrons are confined to a large quantum dot (QD) on the plate's surface. The deformation potential and piezoelectric interactions are considered. By performing standard energy-level statistics we demonstrate that the spectral fluctuations exhibit the same distributions as those of the Gaussian Orthogonal Ensemble (GOE) or the Gaussian Unitary Ensemble (GUE), therefore evidencing the emergence of quantum chaos. That is verified for a large range of material and geometry parameters. In particular, the GUE statistics occurs only in the case of a circular QD. It represents an anomalous phenomenon, previously reported for just a small number of systems, since the problem is time-reversal invariant. The obtained results are explained through a detailed analysis of the Hamiltonian matrix structure.Comment: 14 pages, two column

Anomalous quantum chaotic behavior in nanoelectromechanical structures

It is predicted that for sufficiently strong electron-phonon coupling an anomalous quantum chaotic behavior develops in certain types of suspended electro-mechanical nanostructures, here comprised by a thin cylindrical quantum dot (billiard) on a suspended rectangular dielectric plate. The deformation potential and piezoelectric interactions are considered. As a result of the electron-phonon coupling between the two systems the spectral statistics of the electro-mechanic eigenenergies exhibit an anomalous behavior. If the center of the quantum dot is located at one of the symmetry axes of the rectangular plate, the energy level distributions correspond to the Gaussian Orthogonal Ensemble (GOE), otherwise they belong to the Gaussian Unitary Ensemble (GUE), even though the system is time-reversal invariant.Comment: 4 pages, pdf forma

Casimir force between integrable and chaotic pistons

We have computed numerically the Casimir force between two identical pistons inside a very long cylinder, considering different shapes for the pistons. The pistons can be considered as quantum billiards, whose spectrum determines the vacuum force. The smooth part of the spectrum fixes the force at short distances, and depends only on geometric quantities like the area or perimeter of the piston. However, correcting terms to the force, coming from the oscillating part of the spectrum which is related to the classical dynamics of the billiard, are qualitatively different for classically integrable or chaotic systems. We have performed a detailed numerical analysis of the corresponding Casimir force for pistons with regular and chaotic classical dynamics. For a family of stadium billiards, we have found that the correcting part of the Casimir force presents a sudden change in the transition from regular to chaotic geometries.Comment: 13 pages, 10 figure

Pharmacokinetics of tigecycline in critically ill patients with liver failure defined by maximal liver function capacity test (LiMAx)

Background: In critically ill patients, tigecycline (TGC) remains an important therapeutic option due to its efficacy against multiresistant Gram-positive and Gram-negative bacteria. TGC is metabolized and eliminated predominantly by the liver. Critical illness-induced liver failure may have a profound impact on the pharmacokinetic of TGC. In the present study, we aimed to establish a link between the degree of liver dysfunction and TGC plasma concentration using the novel maximum liver function capacity (LiMAx) test, as a dynamic liver function test. Materials/methods: The prospective study included 33 patients from a surgical ICU with the clinical indication for antibiotic therapy with TGC. The patients received 100 mg loading dose of TGC followed by intermittent standard doses of 50 mg q12. Blood samples for TGC plasma concentration were collected at 0.3, 2, 5, 8 and 11.5 h in a steady-state condition after at least 36 h post-standard dosage. The results were analyzed by means of a high-performance liquid chromatography (HPLC) method. Within the same day, the LiMAx test was carried out and routine blood parameters were measured. Results: Peak plasma concentrations of TGC were significantly higher in patients with severe liver failure (LiMAx  300 µg/kg/h). The pharmacokinetic curves revealed higher values in severe liver failure at any measured point. Moreover, LiMAx and total bilirubin were the only liver-related parameters that correlated with TGC Cmax. Conclusions: The present study demonstrates a high variability of TGC plasma concentrations in critically ill patients. The results show a significant correlation between the degree of liver dysfunction, measured by the LiMAx test, and TGC Cmax. LiMAx test may be a helpful tool beyond others for adjusting the required dosage of hepatic metabolized antibiotics in critically ill patients. Trial registry DRKS—German clinical trials register; Trial registration number: DRKS00008888; Date of registration: 07-17-2015; Date of enrolment of the first participant to the trial: 12-10-201

Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications

Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination

Increased human defensine levels hint at an inflammatory etiology of bisphosphonate-associated osteonecrosis of the jaw: An immunohistological study

<p>Abstract</p> <p>Background</p> <p>Human β-defensins (hBD) are antimicrobial peptides that are an integral part of bone innate immunity. Recently, it could be shown that expression of hBD-1, -2 and -3 were upregulated in cases of osteomyelitis of the jaws. In order to gain insight into the possible impairment of hBD metabolism in bisphosphonate-associated osteonecrosis of the jaws (BONJ), the present exploratory study was designed so as to determine the qualitative and quantitative expression of afore mentioned hBDs in BONJ and infected osteoradionecrosis (ORN), both of which represent inflammatory bone diseases.</p> <p>Methods</p> <p>Bone samples were collected from patients with BONJ (n = 20) and ORN (n = 20). Non-infected healthy bone samples (n = 20) were included as controls. Immunohistological staining in an autostainer was carried out by the (Strept-ABC)-method against hBD-1,-2,-3. Specific positive vs. negative cell reaction of osteocytes (labeling index) near the border of bony resection was determined and counted for quantitative analysis. Number of vital osteocytes vs. empty osteocytes lacunae was compared between groups.</p> <p>Results</p> <p>hBD-1,-2 and -3 could be detected in BONJ as well as ORN and healthy bone samples. Immunoreactivity against hBD-2 and -3 was significantly higher in BONJ than in ORN and healthy jaw bone samples. Number of empty osteocyte lacunae was significantly higher in ORN compared with BONJ (<it>P </it>= 0.001).</p> <p>Conclusion</p> <p>Under the condition of BONJ an increased expression of hBD-1,-2,-3 is detectable, similarly to the recently described upregulation of defensins in chronically infected jaw bones. It remains still unclear how these findings may relate to the pathoetiology of these diseases and whether this is contributing to the development of BONJ and ORN or simply an after effect of the disease.</p